research paper about writer

• Create account

Forgot your password

Lost your password? Please enter your email address. You will receive a link to create a new password.

Do not have an account ? Create new account

Already have a account ? Log in

We recommend the latest version of Chrome and Firefox for best view

• How it works
• Success Stories
• Testimonials
• Find an expert
• For Small Businesses
• Biotechnology
• Medical Devices
• Pharmaceuticals
• Medical Research
• Scientific Research
• Food & Beverage
• Scientific Writing
• Clinical Trials
• Microbiology
• Data Science & Analytics
• Scientific Consulting
• Statistical Analysis
• Food Science & Technology
• Medical Writing
• Clinical Research Consulting
• Clinical Evaluation Report
• EU MDR Consulting
• Secondary Research
• Literature Search
• Scientific Editing
• My Dashboard

Top Freelance Scientific Writers for Hire

Work with top-rated freelance scientific writers to develop high-quality, authoritative content. get help with research papers, grant proposals, blog articles, and more..

• Choose from hundreds of freelance scientific writers specialized in medical writing, science writing, technical writing, academic writing, grant writing, and more.
• Get a subject matter expert to help you write a research paper and prepare it for publishing in a journal of your choice.
• Consult a specialist for help to write literature reviews, conference proceedings, or how-to manuals.
• Get quick help with translation and content writing from language experts.
• The scope of the service can be fully customized and tailored to your specific requirements.

Flexible, easy payments. 100% Satisfaction Guaranteed. Confidentiality assured.

Pay per project

Pay a fixed rate per project. Set up milestones to pay against for complex projects. Increase the budget and scope at any time.

Pay by the hour

Not sure how long your project will take? Pay an hourly rate, with the flexibility to increase the number of hours as you go along.

Pay when you're satisfied

Your money is housed safely on Kolabtree. Release the funds only when you're completely satisfied with the freelancer’s work.

Safe and secure

Our T&C include a default confidentiality clause. However, you can easily upload and sign custom agreements with freelancers.

• 01 Start your project Describe your project, and select the service you need.
• 02 Choose an expert You will receive proposals from experts. Choose an expert based on expertise, price, and other criteria.
• 03 Collaborate Sign NDAs, set goals, and work closely with your chosen expert to get your desired output.
• Job done! Verify the project is complete to your satisfaction and release the payment to the expert.

Cannabis genetic categorization

Writing & editing.

A cannabis researcher hired a plant diversity expert for writing a report on the categorization of the cannabis plant.

Write a ‘How to’ guide

Writing & editing education.

An online technology publication hired a data scientist & writer to develop a 'how-to' guide on data analysis.

Prepare a paper for journal publication

A venture capitalist hired a US-based physicist for help editing a paper and selecting the right journal for publication.

• Technical & Scientic Writing
• Scientific Proofreading
• Medical Content Writing
• Grant Writing
• Systematic Literature Review
• Healthcare Communications
• Manuscript Writing
• Science Communication
• Visual Communication
• Journal Writing
• Medical Copywriting

We will be in touch with you via email/call in the next 8 hours.

Frequently Asked Questions

[email protected]

• Data Scientists & Analytics
• Statistical Review
• Food Science
• Clinical Evaluation Report Writing
• Medical Device Consulting
• Scientific Proofreading & Editing
• Biotechnology and Bioengineering
• Clinical Study Reports
• Manuscript & Journal Article Writing
• Technical & Scientific Writing
• Biomedical Engineering
• Clinical Trial Protocol Writing
• Medical Affairs
• MDR Consulting
• Medical Sciences

Cactus Communications Limited, 15-19 Bloomsbury Way, Holborn, London WC1A 2TH, United Kingdom

© 2024 Cactus Communications Limited, UK. All Rights Reserved

How To Write A Research Paper

Step-By-Step Tutorial With Examples + FREE Template

By: Derek Jansen (MBA) | Expert Reviewer: Dr Eunice Rautenbach | March 2024

For many students, crafting a strong research paper from scratch can feel like a daunting task – and rightly so! In this post, we’ll unpack what a research paper is, what it needs to do , and how to write one – in three easy steps. 🙂 

Overview: Writing A Research Paper

What (exactly) is a research paper.

• How to write a research paper
• Stage 1 : Topic & literature search
• Stage 2 : Structure & outline
• Stage 3 : Iterative writing
• Key takeaways

Let’s start by asking the most important question, “ What is a research paper? ”.

Simply put, a research paper is a scholarly written work where the writer (that’s you!) answers a specific question (this is called a research question ) through evidence-based arguments . Evidence-based is the keyword here. In other words, a research paper is different from an essay or other writing assignments that draw from the writer’s personal opinions or experiences. With a research paper, it’s all about building your arguments based on evidence (we’ll talk more about that evidence a little later).

Now, it’s worth noting that there are many different types of research papers , including analytical papers (the type I just described), argumentative papers, and interpretative papers. Here, we’ll focus on analytical papers , as these are some of the most common – but if you’re keen to learn about other types of research papers, be sure to check out the rest of the blog .

With that basic foundation laid, let’s get down to business and look at how to write a research paper .

Overview: The 3-Stage Process

While there are, of course, many potential approaches you can take to write a research paper, there are typically three stages to the writing process. So, in this tutorial, we’ll present a straightforward three-step process that we use when working with students at Grad Coach.

These three steps are:

• Finding a research topic and reviewing the existing literature
• Developing a provisional structure and outline for your paper, and
• Writing up your initial draft and then refining it iteratively

Let’s dig into each of these.

Need a helping hand?

Step 1: Find a topic and review the literature

As we mentioned earlier, in a research paper, you, as the researcher, will try to answer a question . More specifically, that’s called a research question , and it sets the direction of your entire paper. What’s important to understand though is that you’ll need to answer that research question with the help of high-quality sources – for example, journal articles, government reports, case studies, and so on. We’ll circle back to this in a minute.

The first stage of the research process is deciding on what your research question will be and then reviewing the existing literature (in other words, past studies and papers) to see what they say about that specific research question. In some cases, your professor may provide you with a predetermined research question (or set of questions). However, in many cases, you’ll need to find your own research question within a certain topic area.

Finding a strong research question hinges on identifying a meaningful research gap – in other words, an area that’s lacking in existing research. There’s a lot to unpack here, so if you wanna learn more, check out the plain-language explainer video below.

Once you’ve figured out which question (or questions) you’ll attempt to answer in your research paper, you’ll need to do a deep dive into the existing literature – this is called a “ literature search ”. Again, there are many ways to go about this, but your most likely starting point will be Google Scholar .

If you’re new to Google Scholar, think of it as Google for the academic world. You can start by simply entering a few different keywords that are relevant to your research question and it will then present a host of articles for you to review. What you want to pay close attention to here is the number of citations for each paper – the more citations a paper has, the more credible it is (generally speaking – there are some exceptions, of course).

Ideally, what you’re looking for are well-cited papers that are highly relevant to your topic. That said, keep in mind that citations are a cumulative metric , so older papers will often have more citations than newer papers – just because they’ve been around for longer. So, don’t fixate on this metric in isolation – relevance and recency are also very important.

Beyond Google Scholar, you’ll also definitely want to check out academic databases and aggregators such as Science Direct, PubMed, JStor and so on. These will often overlap with the results that you find in Google Scholar, but they can also reveal some hidden gems – so, be sure to check them out.

Once you’ve worked your way through all the literature, you’ll want to catalogue all this information in some sort of spreadsheet so that you can easily recall who said what, when and within what context. If you’d like, we’ve got a free literature spreadsheet that helps you do exactly that.

Step 2: Develop a structure and outline

With your research question pinned down and your literature digested and catalogued, it’s time to move on to planning your actual research paper .

It might sound obvious, but it’s really important to have some sort of rough outline in place before you start writing your paper. So often, we see students eagerly rushing into the writing phase, only to land up with a disjointed research paper that rambles on in multiple

Now, the secret here is to not get caught up in the fine details . Realistically, all you need at this stage is a bullet-point list that describes (in broad strokes) what you’ll discuss and in what order. It’s also useful to remember that you’re not glued to this outline – in all likelihood, you’ll chop and change some sections once you start writing, and that’s perfectly okay. What’s important is that you have some sort of roadmap in place from the start.

At this stage you might be wondering, “ But how should I structure my research paper? ”. Well, there’s no one-size-fits-all solution here, but in general, a research paper will consist of a few relatively standardised components:

• Introduction
• Literature review
• Methodology

Let’s take a look at each of these.

First up is the introduction section . As the name suggests, the purpose of the introduction is to set the scene for your research paper. There are usually (at least) four ingredients that go into this section – these are the background to the topic, the research problem and resultant research question , and the justification or rationale. If you’re interested, the video below unpacks the introduction section in more detail. 

The next section of your research paper will typically be your literature review . Remember all that literature you worked through earlier? Well, this is where you’ll present your interpretation of all that content . You’ll do this by writing about recent trends, developments, and arguments within the literature – but more specifically, those that are relevant to your research question . The literature review can oftentimes seem a little daunting, even to seasoned researchers, so be sure to check out our extensive collection of literature review content here .

With the introduction and lit review out of the way, the next section of your paper is the research methodology . In a nutshell, the methodology section should describe to your reader what you did (beyond just reviewing the existing literature) to answer your research question. For example, what data did you collect, how did you collect that data, how did you analyse that data and so on? For each choice, you’ll also need to justify why you chose to do it that way, and what the strengths and weaknesses of your approach were.

Now, it’s worth mentioning that for some research papers, this aspect of the project may be a lot simpler . For example, you may only need to draw on secondary sources (in other words, existing data sets). In some cases, you may just be asked to draw your conclusions from the literature search itself (in other words, there may be no data analysis at all). But, if you are required to collect and analyse data, you’ll need to pay a lot of attention to the methodology section. The video below provides an example of what the methodology section might look like.

By this stage of your paper, you will have explained what your research question is, what the existing literature has to say about that question, and how you analysed additional data to try to answer your question. So, the natural next step is to present your analysis of that data . This section is usually called the “results” or “analysis” section and this is where you’ll showcase your findings.

Depending on your school’s requirements, you may need to present and interpret the data in one section – or you might split the presentation and the interpretation into two sections. In the latter case, your “results” section will just describe the data, and the “discussion” is where you’ll interpret that data and explicitly link your analysis back to your research question. If you’re not sure which approach to take, check in with your professor or take a look at past papers to see what the norms are for your programme.

Alright – once you’ve presented and discussed your results, it’s time to wrap it up . This usually takes the form of the “ conclusion ” section. In the conclusion, you’ll need to highlight the key takeaways from your study and close the loop by explicitly answering your research question. Again, the exact requirements here will vary depending on your programme (and you may not even need a conclusion section at all) – so be sure to check with your professor if you’re unsure.

Step 3: Write and refine

Finally, it’s time to get writing. All too often though, students hit a brick wall right about here… So, how do you avoid this happening to you?

Well, there’s a lot to be said when it comes to writing a research paper (or any sort of academic piece), but we’ll share three practical tips to help you get started.

First and foremost , it’s essential to approach your writing as an iterative process. In other words, you need to start with a really messy first draft and then polish it over multiple rounds of editing. Don’t waste your time trying to write a perfect research paper in one go. Instead, take the pressure off yourself by adopting an iterative approach.

Secondly , it’s important to always lean towards critical writing , rather than descriptive writing. What does this mean? Well, at the simplest level, descriptive writing focuses on the “ what ”, while critical writing digs into the “ so what ” – in other words, the implications . If you’re not familiar with these two types of writing, don’t worry! You can find a plain-language explanation here.

Last but not least, you’ll need to get your referencing right. Specifically, you’ll need to provide credible, correctly formatted citations for the statements you make. We see students making referencing mistakes all the time and it costs them dearly. The good news is that you can easily avoid this by using a simple reference manager . If you don’t have one, check out our video about Mendeley, an easy (and free) reference management tool that you can start using today.

Recap: Key Takeaways

We’ve covered a lot of ground here. To recap, the three steps to writing a high-quality research paper are:

• To choose a research question and review the literature
• To plan your paper structure and draft an outline
• To take an iterative approach to writing, focusing on critical writing and strong referencing

Remember, this is just a b ig-picture overview of the research paper development process and there’s a lot more nuance to unpack. So, be sure to grab a copy of our free research paper template to learn more about how to write a research paper.

You Might Also Like:

Submit a Comment Cancel reply

Your email address will not be published. Required fields are marked *

Save my name, email, and website in this browser for the next time I comment.

• Print Friendly

• How to write a research paper

Last updated

11 January 2024

Reviewed by

With proper planning, knowledge, and framework, completing a research paper can be a fulfilling and exciting experience. 

Though it might initially sound slightly intimidating, this guide will help you embrace the challenge. 

By documenting your findings, you can inspire others and make a difference in your field. Here's how you can make your research paper unique and comprehensive.

• What is a research paper?

Research papers allow you to demonstrate your knowledge and understanding of a particular topic. These papers are usually lengthier and more detailed than typical essays, requiring deeper insight into the chosen topic.

To write a research paper, you must first choose a topic that interests you and is relevant to the field of study. Once you’ve selected your topic, gathering as many relevant resources as possible, including books, scholarly articles, credible websites, and other academic materials, is essential. You must then read and analyze these sources, summarizing their key points and identifying gaps in the current research.

You can formulate your ideas and opinions once you thoroughly understand the existing research. To get there might involve conducting original research, gathering data, or analyzing existing data sets. It could also involve presenting an original argument or interpretation of the existing research.

Writing a successful research paper involves presenting your findings clearly and engagingly, which might involve using charts, graphs, or other visual aids to present your data and using concise language to explain your findings. You must also ensure your paper adheres to relevant academic formatting guidelines, including proper citations and references.

Overall, writing a research paper requires a significant amount of time, effort, and attention to detail. However, it is also an enriching experience that allows you to delve deeply into a subject that interests you and contribute to the existing body of knowledge in your chosen field.

• How long should a research paper be?

Research papers are deep dives into a topic. Therefore, they tend to be longer pieces of work than essays or opinion pieces. 

However, a suitable length depends on the complexity of the topic and your level of expertise. For instance, are you a first-year college student or an experienced professional? 

Also, remember that the best research papers provide valuable information for the benefit of others. Therefore, the quality of information matters most, not necessarily the length. Being concise is valuable.

Following these best practice steps will help keep your process simple and productive:

1. Gaining a deep understanding of any expectations

Before diving into your intended topic or beginning the research phase, take some time to orient yourself. Suppose there’s a specific topic assigned to you. In that case, it’s essential to deeply understand the question and organize your planning and approach in response. Pay attention to the key requirements and ensure you align your writing accordingly. 

This preparation step entails

Deeply understanding the task or assignment

Being clear about the expected format and length

Familiarizing yourself with the citation and referencing requirements 

Understanding any defined limits for your research contribution

Where applicable, speaking to your professor or research supervisor for further clarification

2. Choose your research topic

Select a research topic that aligns with both your interests and available resources. Ideally, focus on a field where you possess significant experience and analytical skills. In crafting your research paper, it's crucial to go beyond summarizing existing data and contribute fresh insights to the chosen area.

Consider narrowing your focus to a specific aspect of the topic. For example, if exploring the link between technology and mental health, delve into how social media use during the pandemic impacts the well-being of college students. Conducting interviews and surveys with students could provide firsthand data and unique perspectives, adding substantial value to the existing knowledge.

When finalizing your topic, adhere to legal and ethical norms in the relevant area (this ensures the integrity of your research, protects participants' rights, upholds intellectual property standards, and ensures transparency and accountability). Following these principles not only maintains the credibility of your work but also builds trust within your academic or professional community.

For instance, in writing about medical research, consider legal and ethical norms , including patient confidentiality laws and informed consent requirements. Similarly, if analyzing user data on social media platforms, be mindful of data privacy regulations, ensuring compliance with laws governing personal information collection and use. Aligning with legal and ethical standards not only avoids potential issues but also underscores the responsible conduct of your research.

3. Gather preliminary research

Once you’ve landed on your topic, it’s time to explore it further. You’ll want to discover more about available resources and existing research relevant to your assignment at this stage. 

This exploratory phase is vital as you may discover issues with your original idea or realize you have insufficient resources to explore the topic effectively. This key bit of groundwork allows you to redirect your research topic in a different, more feasible, or more relevant direction if necessary. 

Spending ample time at this stage ensures you gather everything you need, learn as much as you can about the topic, and discover gaps where the topic has yet to be sufficiently covered, offering an opportunity to research it further. 

4. Define your research question

To produce a well-structured and focused paper, it is imperative to formulate a clear and precise research question that will guide your work. Your research question must be informed by the existing literature and tailored to the scope and objectives of your project. By refining your focus, you can produce a thoughtful and engaging paper that effectively communicates your ideas to your readers.

5. Write a thesis statement

A thesis statement is a one-to-two-sentence summary of your research paper's main argument or direction. It serves as an overall guide to summarize the overall intent of the research paper for you and anyone wanting to know more about the research.

A strong thesis statement is:

Concise and clear: Explain your case in simple sentences (avoid covering multiple ideas). It might help to think of this section as an elevator pitch.

Specific: Ensure that there is no ambiguity in your statement and that your summary covers the points argued in the paper.

Debatable: A thesis statement puts forward a specific argument––it is not merely a statement but a debatable point that can be analyzed and discussed.

Here are three thesis statement examples from different disciplines:

Psychology thesis example: "We're studying adults aged 25-40 to see if taking short breaks for mindfulness can help with stress. Our goal is to find practical ways to manage anxiety better."

Environmental science thesis example: "This research paper looks into how having more city parks might make the air cleaner and keep people healthier. I want to find out if more green spaces means breathing fewer carcinogens in big cities."

UX research thesis example: "This study focuses on improving mobile banking for older adults using ethnographic research, eye-tracking analysis, and interactive prototyping. We investigate the usefulness of eye-tracking analysis with older individuals, aiming to spark debate and offer fresh perspectives on UX design and digital inclusivity for the aging population."

6. Conduct in-depth research

A research paper doesn’t just include research that you’ve uncovered from other papers and studies but your fresh insights, too. You will seek to become an expert on your topic––understanding the nuances in the current leading theories. You will analyze existing research and add your thinking and discoveries.  It's crucial to conduct well-designed research that is rigorous, robust, and based on reliable sources. Suppose a research paper lacks evidence or is biased. In that case, it won't benefit the academic community or the general public. Therefore, examining the topic thoroughly and furthering its understanding through high-quality research is essential. That usually means conducting new research. Depending on the area under investigation, you may conduct surveys, interviews, diary studies , or observational research to uncover new insights or bolster current claims.

7. Determine supporting evidence

Not every piece of research you’ve discovered will be relevant to your research paper. It’s important to categorize the most meaningful evidence to include alongside your discoveries. It's important to include evidence that doesn't support your claims to avoid exclusion bias and ensure a fair research paper.

8. Write a research paper outline

Before diving in and writing the whole paper, start with an outline. It will help you to see if more research is needed, and it will provide a framework by which to write a more compelling paper. Your supervisor may even request an outline to approve before beginning to write the first draft of the full paper. An outline will include your topic, thesis statement, key headings, short summaries of the research, and your arguments.

9. Write your first draft

Once you feel confident about your outline and sources, it’s time to write your first draft. While penning a long piece of content can be intimidating, if you’ve laid the groundwork, you will have a structure to help you move steadily through each section. To keep up motivation and inspiration, it’s often best to keep the pace quick. Stopping for long periods can interrupt your flow and make jumping back in harder than writing when things are fresh in your mind.

10. Cite your sources correctly

It's always a good practice to give credit where it's due, and the same goes for citing any works that have influenced your paper. Building your arguments on credible references adds value and authenticity to your research. In the formatting guidelines section, you’ll find an overview of different citation styles (MLA, CMOS, or APA), which will help you meet any publishing or academic requirements and strengthen your paper's credibility. It is essential to follow the guidelines provided by your school or the publication you are submitting to ensure the accuracy and relevance of your citations.

11. Ensure your work is original

It is crucial to ensure the originality of your paper, as plagiarism can lead to serious consequences. To avoid plagiarism, you should use proper paraphrasing and quoting techniques. Paraphrasing is rewriting a text in your own words while maintaining the original meaning. Quoting involves directly citing the source. Giving credit to the original author or source is essential whenever you borrow their ideas or words. You can also use plagiarism detection tools such as Scribbr or Grammarly to check the originality of your paper. These tools compare your draft writing to a vast database of online sources. If you find any accidental plagiarism, you should correct it immediately by rephrasing or citing the source.

12. Revise, edit, and proofread

One of the essential qualities of excellent writers is their ability to understand the importance of editing and proofreading. Even though it's tempting to call it a day once you've finished your writing, editing your work can significantly improve its quality. It's natural to overlook the weaker areas when you've just finished writing a paper. Therefore, it's best to take a break of a day or two, or even up to a week, to refresh your mind. This way, you can return to your work with a new perspective. After some breathing room, you can spot any inconsistencies, spelling and grammar errors, typos, or missing citations and correct them. 

• The best research paper format 

The format of your research paper should align with the requirements set forth by your college, school, or target publication. 

There is no one “best” format, per se. Depending on the stated requirements, you may need to include the following elements:

Title page: The title page of a research paper typically includes the title, author's name, and institutional affiliation and may include additional information such as a course name or instructor's name. 

Table of contents: Include a table of contents to make it easy for readers to find specific sections of your paper.

Abstract: The abstract is a summary of the purpose of the paper.

Methods : In this section, describe the research methods used. This may include collecting data , conducting interviews, or doing field research .

Results: Summarize the conclusions you drew from your research in this section.

Discussion: In this section, discuss the implications of your research . Be sure to mention any significant limitations to your approach and suggest areas for further research.

Tables, charts, and illustrations: Use tables, charts, and illustrations to help convey your research findings and make them easier to understand.

Works cited or reference page: Include a works cited or reference page to give credit to the sources that you used to conduct your research.

Bibliography: Provide a list of all the sources you consulted while conducting your research.

Dedication and acknowledgments : Optionally, you may include a dedication and acknowledgments section to thank individuals who helped you with your research.

• General style and formatting guidelines

Formatting your research paper means you can submit it to your college, journal, or other publications in compliance with their criteria.

Research papers tend to follow the American Psychological Association (APA), Modern Language Association (MLA), or Chicago Manual of Style (CMOS) guidelines.

Here’s how each style guide is typically used:

Chicago Manual of Style (CMOS):

CMOS is a versatile style guide used for various types of writing. It's known for its flexibility and use in the humanities. CMOS provides guidelines for citations, formatting, and overall writing style. It allows for both footnotes and in-text citations, giving writers options based on their preferences or publication requirements.

American Psychological Association (APA):

APA is common in the social sciences. It’s hailed for its clarity and emphasis on precision. It has specific rules for citing sources, creating references, and formatting papers. APA style uses in-text citations with an accompanying reference list. It's designed to convey information efficiently and is widely used in academic and scientific writing.

Modern Language Association (MLA):

MLA is widely used in the humanities, especially literature and language studies. It emphasizes the author-page format for in-text citations and provides guidelines for creating a "Works Cited" page. MLA is known for its focus on the author's name and the literary works cited. It’s frequently used in disciplines that prioritize literary analysis and critical thinking.

To confirm you're using the latest style guide, check the official website or publisher's site for updates, consult academic resources, and verify the guide's publication date. Online platforms and educational resources may also provide summaries and alerts about any revisions or additions to the style guide.

Citing sources

When working on your research paper, it's important to cite the sources you used properly. Your citation style will guide you through this process. Generally, there are three parts to citing sources in your research paper: 

First, provide a brief citation in the body of your essay. This is also known as a parenthetical or in-text citation. 

Second, include a full citation in the Reference list at the end of your paper. Different types of citations include in-text citations, footnotes, and reference lists. 

In-text citations include the author's surname and the date of the citation. 

Footnotes appear at the bottom of each page of your research paper. They may also be summarized within a reference list at the end of the paper. 

A reference list includes all of the research used within the paper at the end of the document. It should include the author, date, paper title, and publisher listed in the order that aligns with your citation style.

10 research paper writing tips:

Following some best practices is essential to writing a research paper that contributes to your field of study and creates a positive impact.

These tactics will help you structure your argument effectively and ensure your work benefits others:

Clear and precise language:  Ensure your language is unambiguous. Use academic language appropriately, but keep it simple. Also, provide clear takeaways for your audience.

Effective idea separation:  Organize the vast amount of information and sources in your paper with paragraphs and titles. Create easily digestible sections for your readers to navigate through.

Compelling intro:  Craft an engaging introduction that captures your reader's interest. Hook your audience and motivate them to continue reading.

Thorough revision and editing:  Take the time to review and edit your paper comprehensively. Use tools like Grammarly to detect and correct small, overlooked errors.

Thesis precision:  Develop a clear and concise thesis statement that guides your paper. Ensure that your thesis aligns with your research's overall purpose and contribution.

Logical flow of ideas:  Maintain a logical progression throughout the paper. Use transitions effectively to connect different sections and maintain coherence.

Critical evaluation of sources:  Evaluate and critically assess the relevance and reliability of your sources. Ensure that your research is based on credible and up-to-date information.

Thematic consistency:  Maintain a consistent theme throughout the paper. Ensure that all sections contribute cohesively to the overall argument.

Relevant supporting evidence:  Provide concise and relevant evidence to support your arguments. Avoid unnecessary details that may distract from the main points.

Embrace counterarguments:  Acknowledge and address opposing views to strengthen your position. Show that you have considered alternative arguments in your field.

7 research tips 

If you want your paper to not only be well-written but also contribute to the progress of human knowledge, consider these tips to take your paper to the next level:

Selecting the appropriate topic: The topic you select should align with your area of expertise, comply with the requirements of your project, and have sufficient resources for a comprehensive investigation.

Use academic databases: Academic databases such as PubMed, Google Scholar, and JSTOR offer a wealth of research papers that can help you discover everything you need to know about your chosen topic.

Critically evaluate sources: It is important not to accept research findings at face value. Instead, it is crucial to critically analyze the information to avoid jumping to conclusions or overlooking important details. A well-written research paper requires a critical analysis with thorough reasoning to support claims.

Diversify your sources: Expand your research horizons by exploring a variety of sources beyond the standard databases. Utilize books, conference proceedings, and interviews to gather diverse perspectives and enrich your understanding of the topic.

Take detailed notes: Detailed note-taking is crucial during research and can help you form the outline and body of your paper.

Stay up on trends: Keep abreast of the latest developments in your field by regularly checking for recent publications. Subscribe to newsletters, follow relevant journals, and attend conferences to stay informed about emerging trends and advancements. 

Engage in peer review: Seek feedback from peers or mentors to ensure the rigor and validity of your research . Peer review helps identify potential weaknesses in your methodology and strengthens the overall credibility of your findings.

• The real-world impact of research papers

Writing a research paper is more than an academic or business exercise. The experience provides an opportunity to explore a subject in-depth, broaden one's understanding, and arrive at meaningful conclusions. With careful planning, dedication, and hard work, writing a research paper can be a fulfilling and enriching experience contributing to advancing knowledge.

How do I publish my research paper? 

Many academics wish to publish their research papers. While challenging, your paper might get traction if it covers new and well-written information. To publish your research paper, find a target publication, thoroughly read their guidelines, format your paper accordingly, and send it to them per their instructions. You may need to include a cover letter, too. After submission, your paper may be peer-reviewed by experts to assess its legitimacy, quality, originality, and methodology. Following review, you will be informed by the publication whether they have accepted or rejected your paper. 

What is a good opening sentence for a research paper? 

Beginning your research paper with a compelling introduction can ensure readers are interested in going further. A relevant quote, a compelling statistic, or a bold argument can start the paper and hook your reader. Remember, though, that the most important aspect of a research paper is the quality of the information––not necessarily your ability to storytell, so ensure anything you write aligns with your goals.

Research paper vs. a research proposal—what’s the difference?

While some may confuse research papers and proposals, they are different documents. 

A research proposal comes before a research paper. It is a detailed document that outlines an intended area of exploration. It includes the research topic, methodology, timeline, sources, and potential conclusions. Research proposals are often required when seeking approval to conduct research. 

A research paper is a summary of research findings. A research paper follows a structured format to present those findings and construct an argument or conclusion.

Should you be using a customer insights hub?

Do you want to discover previous research faster?

Do you share your research findings with others?

Do you analyze research data?

Start for free today, add your research, and get to key insights faster

Editor’s picks

Last updated: 13 April 2023

Last updated: 14 February 2024

Last updated: 27 January 2024

Last updated: 18 April 2023

Last updated: 8 February 2023

Last updated: 23 January 2024

Last updated: 30 January 2024

Last updated: 7 February 2023

Last updated: 18 May 2023

Last updated: 31 January 2024

Last updated: 13 May 2024

Latest articles

Related topics, .css-je19u9{-webkit-align-items:flex-end;-webkit-box-align:flex-end;-ms-flex-align:flex-end;align-items:flex-end;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:row;-ms-flex-direction:row;flex-direction:row;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:center;-ms-flex-pack:center;-webkit-justify-content:center;justify-content:center;row-gap:0;text-align:center;max-width:671px;}@media (max-width: 1079px){.css-je19u9{max-width:400px;}.css-je19u9>span{white-space:pre;}}@media (max-width: 799px){.css-je19u9{max-width:400px;}.css-je19u9>span{white-space:pre;}} decide what to .css-1kiodld{max-height:56px;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}@media (max-width: 1079px){.css-1kiodld{display:none;}} build next, decide what to build next.

Users report unexpectedly high data usage, especially during streaming sessions.

Users find it hard to navigate from the home page to relevant playlists in the app.

It would be great to have a sleep timer feature, especially for bedtime listening.

I need better filters to find the songs or artists I’m looking for.

• 10 research paper

Log in or sign up

Get started for free

How to Write a Research Paper

Use the links below to jump directly to any section of this guide:

Research Paper Fundamentals

How to choose a topic or question, how to create a working hypothesis or thesis, common research paper methodologies, how to gather and organize evidence , how to write an outline for your research paper, how to write a rough draft, how to revise your draft, how to produce a final draft, resources for teachers .

It is not fair to say that no one writes anymore. Just about everyone writes text messages, brief emails, or social media posts every single day. Yet, most people don't have a lot of practice with the formal, organized writing required for a good academic research paper. This guide contains links to a variety of resources that can help demystify the process. Some of these resources are intended for teachers; they contain exercises, activities, and teaching strategies. Other resources are intended for direct use by students who are struggling to write papers, or are looking for tips to make the process go more smoothly.

The resources in this section are designed to help students understand the different types of research papers, the general research process, and how to manage their time. Below, you'll find links from university writing centers, the trusted Purdue Online Writing Lab, and more.

What is an Academic Research Paper?

"Genre and the Research Paper" (Purdue OWL)

There are different types of research papers. Different types of scholarly questions will lend themselves to one format or another. This is a brief introduction to the two main genres of research paper: analytic and argumentative. 

"7 Most Popular Types of Research Papers" (Personal-writer.com)

This resource discusses formats that high school students commonly encounter, such as the compare and contrast essay and the definitional essay. Please note that the inclusion of this link is not an endorsement of this company's paid service.

How to Prepare and Plan Out Writing a Research Paper

Teachers can give their students a step-by-step guide like these to help them understand the different steps of the research paper process. These guides can be combined with the time management tools in the next subsection to help students come up with customized calendars for completing their papers.

"Ten Steps for Writing Research Papers" (American University)  

This resource from American University is a comprehensive guide to the research paper writing process, and includes examples of proper research questions and thesis topics.

"Steps in Writing a Research Paper" (SUNY Empire State College)

This guide breaks the research paper process into 11 steps. Each "step" links to a separate page, which describes the work entailed in completing it.

How to Manage Time Effectively

The links below will help students determine how much time is necessary to complete a paper. If your sources are not available online or at your local library, you'll need to leave extra time for the Interlibrary Loan process. Remember that, even if you do not need to consult secondary sources, you'll still need to leave yourself ample time to organize your thoughts.

"Research Paper Planner: Timeline" (Baylor University)

This interactive resource from Baylor University creates a suggested writing schedule based on how much time a student has to work on the assignment.

"Research Paper Planner" (UCLA)

UCLA's library offers this step-by-step guide to the research paper writing process, which also includes a suggested planning calendar.

There's a reason teachers spend a long time talking about choosing a good topic. Without a good topic and a well-formulated research question, it is almost impossible to write a clear and organized paper. The resources below will help you generate ideas and formulate precise questions.

"How to Select a Research Topic" (Univ. of Michigan-Flint)

This resource is designed for college students who are struggling to come up with an appropriate topic. A student who uses this resource and still feels unsure about his or her topic should consult the course instructor for further personalized assistance.

"25 Interesting Research Paper Topics to Get You Started" (Kibin)

This resource, which is probably most appropriate for high school students, provides a list of specific topics to help get students started. It is broken into subsections, such as "paper topics on local issues."

"Writing a Good Research Question" (Grand Canyon University)

This introduction to research questions includes some embedded videos, as well as links to scholarly articles on research questions. This resource would be most appropriate for teachers who are planning lessons on research paper fundamentals.

"How to Write a Research Question the Right Way" (Kibin)

This student-focused resource provides more detail on writing research questions. The language is accessible, and there are embedded videos and examples of good and bad questions.

It is important to have a rough hypothesis or thesis in mind at the beginning of the research process. People who have a sense of what they want to say will have an easier time sorting through scholarly sources and other information. The key, of course, is not to become too wedded to the draft hypothesis or thesis. Just about every working thesis gets changed during the research process.

CrashCourse Video: "Sociology Research Methods" (YouTube)

Although this video is tailored to sociology students, it is applicable to students in a variety of social science disciplines. This video does a good job demonstrating the connection between the brainstorming that goes into selecting a research question and the formulation of a working hypothesis.

"How to Write a Thesis Statement for an Analytical Essay" (YouTube)

Students writing analytical essays will not develop the same type of working hypothesis as students who are writing research papers in other disciplines. For these students, developing the working thesis may happen as a part of the rough draft (see the relevant section below). 

"Research Hypothesis" (Oakland Univ.)

This resource provides some examples of hypotheses in social science disciplines like Political Science and Criminal Justice. These sample hypotheses may also be useful for students in other soft social sciences and humanities disciplines like History.

When grading a research paper, instructors look for a consistent methodology. This section will help you understand different methodological approaches used in research papers. Students will get the most out of these resources if they use them to help prepare for conversations with teachers or discussions in class.

"Types of Research Designs" (USC)

A "research design," used for complex papers, is related to the paper's method. This resource contains introductions to a variety of popular research designs in the social sciences. Although it is not the most intuitive site to read, the information here is very valuable. 

"Major Research Methods" (YouTube)

Although this video is a bit on the dry side, it provides a comprehensive overview of the major research methodologies in a format that might be more accessible to students who have struggled with textbooks or other written resources.

"Humanities Research Strategies" (USC)

This is a portal where students can learn about four methodological approaches for humanities papers: Historical Methodologies, Textual Criticism, Conceptual Analysis, and the Synoptic method.

"Selected Major Social Science Research Methods: Overview" (National Academies Press)

This appendix from the book  Using Science as Evidence in Public Policy , printed by National Academies Press, introduces some methods used in social science papers.

"Organizing Your Social Sciences Research Paper: 6. The Methodology" (USC)

This resource from the University of Southern California's library contains tips for writing a methodology section in a research paper.

How to Determine the Best Methodology for You

Anyone who is new to writing research papers should be sure to select a method in consultation with their instructor. These resources can be used to help prepare for that discussion. They may also be used on their own by more advanced students.

"Choosing Appropriate Research Methodologies" (Palgrave Study Skills)

This friendly and approachable resource from Palgrave Macmillan can be used by students who are just starting to think about appropriate methodologies.

"How to Choose Your Research Methods" (NFER (UK))

This is another approachable resource students can use to help narrow down the most appropriate methods for their research projects.

The resources in this section introduce the process of gathering scholarly sources and collecting evidence. You'll find a range of material here, from introductory guides to advanced explications best suited to college students. Please consult the LitCharts  How to Do Academic Research guide for a more comprehensive list of resources devoted to finding scholarly literature.

Google Scholar

Students who have access to library websites with detailed research guides should start there, but people who do not have access to those resources can begin their search for secondary literature here.

"Gathering Appropriate Information" (Texas Gateway)

This resource from the Texas Gateway for online resources introduces students to the research process, and contains interactive exercises. The level of complexity is suitable for middle school, high school, and introductory college classrooms.

"An Overview of Quantitative and Qualitative Data Collection Methods" (NSF)

This PDF from the National Science Foundation goes into detail about best practices and pitfalls in data collection across multiple types of methodologies.

"Social Science Methods for Data Collection and Analysis" (Swiss FIT)

This resource is appropriate for advanced undergraduates or teachers looking to create lessons on research design and data collection. It covers techniques for gathering data via interviews, observations, and other methods.

"Collecting Data by In-depth Interviewing" (Leeds Univ.)

This resource contains enough information about conducting interviews to make it useful for teachers who want to create a lesson plan, but is also accessible enough for college juniors or seniors to make use of it on their own.

There is no "one size fits all" outlining technique. Some students might devote all their energy and attention to the outline in order to avoid the paper. Other students may benefit from being made to sit down and organize their thoughts into a lengthy sentence outline. The resources in this section include strategies and templates for multiple types of outlines. 

"Topic vs. Sentence Outlines" (UC Berkeley)

This resource introduces two basic approaches to outlining: the shorter topic-based approach, and the longer, more detailed sentence-based approach. This resource also contains videos on how to develop paper paragraphs from the sentence-based outline.

"Types of Outlines and Samples" (Purdue OWL)

The Purdue Online Writing Lab's guide is a slightly less detailed discussion of different types of outlines. It contains several sample outlines.

"Writing An Outline" (Austin C.C.)

This resource from a community college contains sample outlines from an American history class that students can use as models.

"How to Structure an Outline for a College Paper" (YouTube)

This brief (sub-2 minute) video from the ExpertVillage YouTube channel provides a model of outline writing for students who are struggling with the idea.

"Outlining" (Harvard)

This is a good resource to consult after completing a draft outline. It offers suggestions for making sure your outline avoids things like unnecessary repetition.

As with outlines, rough drafts can take on many different forms. These resources introduce teachers and students to the various approaches to writing a rough draft. This section also includes resources that will help you cite your sources appropriately according to the MLA, Chicago, and APA style manuals.

"Creating a Rough Draft for a Research Paper" (Univ. of Minnesota)

This resource is useful for teachers in particular, as it provides some suggested exercises to help students with writing a basic rough draft. 

Rough Draft Assignment (Duke of Definition)

This sample assignment, with a brief list of tips, was developed by a high school teacher who runs a very successful and well-reviewed page of educational resources.

"Creating the First Draft of Your Research Paper" (Concordia Univ.)

This resource will be helpful for perfectionists or procrastinators, as it opens by discussing the problem of avoiding writing. It also provides a short list of suggestions meant to get students writing.

Using Proper Citations

There is no such thing as a rough draft of a scholarly citation. These links to the three major citation guides will ensure that your citations follow the correct format. Please consult the LitCharts How to Cite Your Sources guide for more resources.

Chicago Manual of Style Citation Guide

Some call  The Chicago Manual of Style , which was first published in 1906, "the editors' Bible." The manual is now in its 17th edition, and is popular in the social sciences, historical journals, and some other fields in the humanities.

APA Citation Guide

According to the American Psychological Association, this guide was developed to aid reading comprehension, clarity of communication, and to reduce bias in language in the social and behavioral sciences. Its first full edition was published in 1952, and it is now in its sixth edition.

MLA Citation Guide

The Modern Language Association style is used most commonly within the liberal arts and humanities. The  MLA Style Manual and Guide to Scholarly Publishing  was first published in 1985 and (as of 2008) is in its third edition.

Any professional scholar will tell you that the best research papers are made in the revision stage. No matter how strong your research question or working thesis, it is not possible to write a truly outstanding paper without devoting energy to revision. These resources provide examples of revision exercises for the classroom, as well as tips for students working independently.

"The Art of Revision" (Univ. of Arizona)

This resource provides a wealth of information and suggestions for both students and teachers. There is a list of suggested exercises that teachers might use in class, along with a revision checklist that is useful for teachers and students alike.

"Script for Workshop on Revision" (Vanderbilt University)

Vanderbilt's guide for leading a 50-minute revision workshop can serve as a model for teachers who wish to guide students through the revision process during classtime. 

"Revising Your Paper" (Univ. of Washington)

This detailed handout was designed for students who are beginning the revision process. It discusses different approaches and methods for revision, and also includes a detailed list of things students should look for while they revise.

"Revising Drafts" (UNC Writing Center)

This resource is designed for students and suggests things to look for during the revision process. It provides steps for the process and has a FAQ for students who have questions about why it is important to revise.

Conferencing with Writing Tutors and Instructors

No writer is so good that he or she can't benefit from meeting with instructors or peer tutors. These resources from university writing, learning, and communication centers provide suggestions for how to get the most out of these one-on-one meetings.

"Getting Feedback" (UNC Writing Center)

This very helpful resource talks about how to ask for feedback during the entire writing process. It contains possible questions that students might ask when developing an outline, during the revision process, and after the final draft has been graded.

"Prepare for Your Tutoring Session" (Otis College of Art and Design)

This guide from a university's student learning center contains a lot of helpful tips for getting the most out of working with a writing tutor.

"The Importance of Asking Your Professor" (Univ. of Waterloo)

This article from the university's Writing and Communication Centre's blog contains some suggestions for how and when to get help from professors and Teaching Assistants.

Once you've revised your first draft, you're well on your way to handing in a polished paper. These resources—each of them produced by writing professionals at colleges and universities—outline the steps required in order to produce a final draft. You'll find proofreading tips and checklists in text and video form.

"Developing a Final Draft of a Research Paper" (Univ. of Minnesota)

While this resource contains suggestions for revision, it also features a couple of helpful checklists for the last stages of completing a final draft.

Basic Final Draft Tips and Checklist (Univ. of Maryland-University College)

This short and accessible resource, part of UMUC's very thorough online guide to writing and research, contains a very basic checklist for students who are getting ready to turn in their final drafts.

Final Draft Checklist (Everett C.C.)

This is another accessible final draft checklist, appropriate for both high school and college students. It suggests reading your essay aloud at least once.

"How to Proofread Your Final Draft" (YouTube)

This video (approximately 5 minutes), produced by Eastern Washington University, gives students tips on proofreading final drafts.

"Proofreading Tips" (Georgia Southern-Armstrong)

This guide will help students learn how to spot common errors in their papers. It suggests focusing on content and editing for grammar and mechanics.

This final set of resources is intended specifically for high school and college instructors. It provides links to unit plans and classroom exercises that can help improve students' research and writing skills. You'll find resources that give an overview of the process, along with activities that focus on how to begin and how to carry out research. 

"Research Paper Complete Resources Pack" (Teachers Pay Teachers)

This packet of assignments, rubrics, and other resources is designed for high school students. The resources in this packet are aligned to Common Core standards.

"Research Paper—Complete Unit" (Teachers Pay Teachers)

This packet of assignments, notes, PowerPoints, and other resources has a 4/4 rating with over 700 ratings. It is designed for high school teachers, but might also be useful to college instructors who work with freshmen.

"Teaching Students to Write Good Papers" (Yale)

This resource from Yale's Center for Teaching and Learning is designed for college instructors, and it includes links to appropriate activities and exercises.

"Research Paper Writing: An Overview" (CUNY Brooklyn)

CUNY Brooklyn offers this complete lesson plan for introducing students to research papers. It includes an accompanying set of PowerPoint slides.

"Lesson Plan: How to Begin Writing a Research Paper" (San Jose State Univ.)

This lesson plan is designed for students in the health sciences, so teachers will have to modify it for their own needs. It includes a breakdown of the brainstorming, topic selection, and research question process. 

"Quantitative Techniques for Social Science Research" (Univ. of Pittsburgh)

This is a set of PowerPoint slides that can be used to introduce students to a variety of quantitative methods used in the social sciences.

• PDFs for all 136 Lit Terms we cover
• Downloads of 1934 LitCharts Lit Guides
• Teacher Editions for every Lit Guide
• Explanations and citation info for 40,762 quotes across 1934 books
• Downloadable (PDF) line-by-line translations of every Shakespeare play

Need something? Request a new guide .

How can we improve? Share feedback .

LitCharts is hiring!

Writing a Research Paper

This page lists some of the stages involved in writing a library-based research paper.

Although this list suggests that there is a simple, linear process to writing such a paper, the actual process of writing a research paper is often a messy and recursive one, so please use this outline as a flexible guide.

Discovering, Narrowing, and Focusing a Researchable Topic

• Try to find a topic that truly interests you
• Try writing your way to a topic
• Talk with your course instructor and classmates about your topic
• Pose your topic as a question to be answered or a problem to be solved

Finding, Selecting, and Reading Sources

You will need to look at the following types of sources:

• library catalog, periodical indexes, bibliographies, suggestions from your instructor
• primary vs. secondary sources
• journals, books, other documents

Grouping, Sequencing, and Documenting Information

The following systems will help keep you organized:

• a system for noting sources on bibliography cards
• a system for organizing material according to its relative importance
• a system for taking notes

Writing an Outline and a Prospectus for Yourself

Consider the following questions:

• What is the topic?
• Why is it significant?
• What background material is relevant?
• What is my thesis or purpose statement?
• What organizational plan will best support my purpose?

Writing the Introduction

In the introduction you will need to do the following things:

• present relevant background or contextual material
• define terms or concepts when necessary
• explain the focus of the paper and your specific purpose
• reveal your plan of organization

Writing the Body

• Use your outline and prospectus as flexible guides
• Build your essay around points you want to make (i.e., don’t let your sources organize your paper)
• Integrate your sources into your discussion
• Summarize, analyze, explain, and evaluate published work rather than merely reporting it
• Move up and down the “ladder of abstraction” from generalization to varying levels of detail back to generalization

Writing the Conclusion

• If the argument or point of your paper is complex, you may need to summarize the argument for your reader.
• If prior to your conclusion you have not yet explained the significance of your findings or if you are proceeding inductively, use the end of your paper to add your points up, to explain their significance.
• Move from a detailed to a general level of consideration that returns the topic to the context provided by the introduction.
• Perhaps suggest what about this topic needs further research.

Revising the Final Draft

• Check overall organization : logical flow of introduction, coherence and depth of discussion in body, effectiveness of conclusion.
• Paragraph level concerns : topic sentences, sequence of ideas within paragraphs, use of details to support generalizations, summary sentences where necessary, use of transitions within and between paragraphs.
• Sentence level concerns: sentence structure, word choices, punctuation, spelling.
• Documentation: consistent use of one system, citation of all material not considered common knowledge, appropriate use of endnotes or footnotes, accuracy of list of works cited.

Academic and Professional Writing

This is an accordion element with a series of buttons that open and close related content panels.

Analysis Papers

Reading Poetry

A Short Guide to Close Reading for Literary Analysis

Using Literary Quotations

Play Reviews

Writing a Rhetorical Précis to Analyze Nonfiction Texts

Incorporating Interview Data

Grant Proposals

Planning and Writing a Grant Proposal: The Basics

Additional Resources for Grants and Proposal Writing

Job Materials and Application Essays

Writing Personal Statements for Ph.D. Programs

• Before you begin: useful tips for writing your essay
• Guided brainstorming exercises
• Get more help with your essay
• Frequently Asked Questions

Resume Writing Tips

CV Writing Tips

Cover Letters

Business Letters

Proposals and Dissertations

Resources for Proposal Writers

Resources for Dissertators

Research Papers

Planning and Writing Research Papers

Quoting and Paraphrasing

Writing Annotated Bibliographies

Creating Poster Presentations

Writing an Abstract for Your Research Paper

Thank-You Notes

Advice for Students Writing Thank-You Notes to Donors

Reading for a Review

Critical Reviews

Writing a Review of Literature

Scientific Reports

Scientific Report Format

Sample Lab Assignment

Writing for the Web

Writing an Effective Blog Post

Writing for Social Media: A Guide for Academics

Research paper writing service

1k+ adept writers at your service

Leave your research paper worries to us.

Trusted by 1,5M+ happy customers

Our top-tier research paper writers

Check out our vast selection of talented academic writers to find the best fit for your research paper needs.

Thinking twice about ordering? Let's clear things up!

Can your team write my research paper, maintaining a high level of quality?

Our global team of native-speaking writers holds BA, MA, or Ph.D. degrees from reputable universities. They carefully follow your professor's guidelines, turning years of experience into compelling papers of any format.

Do you ensure transparent transactions?

Your financial security is paramount at EssayPro. All payments are processed through secure gateways, ensuring risk-free and seamless transactions. Funds remain in your balance until you approve your final paper and release them to your writer.

Will a human exclusively craft my paper?

Every assignment you receive is penned from scratch by our skilled writers, not AI content generators. They meticulously craft each paper, using credible sources and adhering to your selected style guide. Afterward, each paper undergoes rigorous checks via sophisticated tools to ensure at least 96% originality.

Might my professors know I've received your help?

Rest assured, we prioritize your privacy. Your security is fortified by top-tier encryption, a strict Privacy Policy, and reputable payment gateways, ensuring the safekeeping of your data. We are committed to maintaining your confidentiality at all times.

Top reasons to pick our research paper service

Original content commitment.

Originality is our motto. Our writers create content from the ground up, consulting only credible sources.

Always here for you

Questions? Concerns? Ask anything, anytime. Our 24/7 support team is here to assist.

Quality and expertise

Quality meets expertise here. Your paper will be sculpted by professionals with relevant academic acumen.

Prompt delivery

Deadlines looming? Fear not! We guarantee prompt delivery for every order.

Your research paper is just three steps away

1. share your paper details.

Fill out a short form specifying your writing needs. Provide us with your instructions to understand how to best assist you.

2. Pick a research paper writer

Immerse yourself in our pool of talented writers. Explore their profiles and identify your ideal academic ally. Your funds remain secure until you approve the final work.

3. Enjoy the results

Once your paper is ready, we'll drop an email your way. Feel free to request tweaks from your writer before releasing payment.

Unbiased customer feedback about EssayPro

Explore peer reviews and learn about our service's unique advantages.

What do we guarantee our customers

Ask for our research paper writing assistance and unlock these cool features at no additional cost.

Caring support 24/7

Got an urgent question in the middle of the night? No problem! Our stellar support team is here for you any time of day. Shoot us a message and get a response within minutes.

No limits on revisions

We don't just handle your research paper writing but refine your assignment to perfection. Ask for free edits for 14 or 30 days after paper completion, depending on your order details.

Call for help with research paper anytime you need

Frequently asked question, is your research paper service legal, who are your writers, which referencing styles can you cover, how do your experts write my research paper, can you help me if i need help with a research paper on a complex topic, how much do your services cost, can i make changes to my research paper after it's completed, custom research paper writing service, essay pro: who are we.

EssayPro is a market-dominating research paper writing service that cares about students' success. We offer high-quality solutions to all kinds of academic woes, helping our customers manage their assignments without extra stress. Our large team of seasoned academic pros is always on standby to handle your daunting papers.

Having helped thousands of customers with their requests, we've become true pros in catering to students' needs. No matter how intricate, urgent, or lengthy your assignment is, we've got your back! All you have to do is shoot us a message saying, "Write my research paper for me." Our highly skilled writers will take it from there. Sit back and relax while our gifted wordsmiths craft a one-of-a-kind academic piece tailored to your needs.

How does an essay differ from a research paper?

Essays and research papers are two drastically different types of assignments. And understanding the difference between them is the key to academic success.

An essay is a shorter academic piece that covers a specific topic. Typically, it consists of three parts - introduction, main body, and conclusion. The introduction unveils the main topic and presents the key points of the essay. The main body supports these statements with examples and evidence, while the conclusion sums up the whole work and includes insights.

On the other hand, a research paper is a more complex work that involves an in-depth study of a specific topic. Usually, it also includes the methodology of research, literature reviews, results of the study, and a proper conclusion. In this case, the assistance of a seasoned research paper writer can significantly improve your performance.

Place a "write my research essay" request on our platform and leave your tedious assignment to seasoned experts.

Ask for our aid and ditch academic stress

Tired of never-ending assignments? Anxious about pressing deadlines? Thinking, "Who can help me write my research paper?" is only natural in this situation. Fortunately, we can offer an easy yet efficient solution to your academic struggles. Our personalized research paper writing services are designed to help you manage your assignments without extra stress.

Place your order today and rest easy, knowing your assignment is in the safe hands of a genuine pro. Our carefully vetted writers are true masters of their craft. Having completed thousands of similar orders, they know how to handle the most intricate research paper requests. Plus, all our helpers have an unwavering commitment to quality and deadlines. In most cases, you'll receive your highly unique academic piece hours or even days before your due date.

Still have doubts? Check out the testimonials from our satisfied customers or ask our stellar customer support for clarifications.

Offload your research paper to EssayPro and forget about assignment anxiety once and for all!

What is a research paper?

A research paper is one of the most complicated assignments students can be tasked with. Crafting this paper involves conducting in-depth research and presenting your arguments, hence the name. Many learners struggle with this assignment as it requires a deep understanding of the subject, hours of focus, and much dedication. That's why our research paper writing service exists.

Our key goal is to simplify your academic journey, offering prompt and qualified assistance with daunting tasks. Let our skilled experts take care of your research paper and enjoy guaranteed quality and comfort. When you entrust your assignment to one of our pros, you'll get a properly-composed academic piece that includes:

• Interview citations, observations, questionnaires, and surveys
• Proved or rejected hypothesis
• Comprehensive research of the specific problem

Depending on the complexity of your research, you can get a finalized paper in just a few hours.

Request our research paper writing services and unlock these perks

EssayPro doesn't just offer high-quality research paper writing services. We provide students with comprehensive solutions to all their academic troubles and tailored assistance every step of the way.

Thousands of learners offload their assignments to us, knowing they'll get quality content before their deadline. Our easy-to-navigate platform allows for quick 3-step orders, tight security, and safe payments via Visa, MasterCard, Maestro, Discover, Diners Club International, or American Express.

Our writing team is made up of strictly top-level specialists with years of experience and higher education degrees. Delegate your assignment to EssayPro and expect nothing but premium quality!

Signs you need our assistance

• You can't comprehend your professor's guidelines
• You struggle to find all the necessary resources for your paper
• Your deadline is approaching, and you can't finish your assignment on time
• You need another pair of eyes to proofread or edit your paper
• You need help expanding your research
• The topic of your research is too obscure or complex
• The outline doesn't match the research
• The structure is not coherent
• You have trouble formatting your paper according to your uni's standards

If any of these sound familiar to you, then EssayPro is your one-stop research writing assistance shop.

Purdue Online Writing Lab Purdue OWL® College of Liberal Arts

Writing a Research Paper

Welcome to the Purdue OWL

This page is brought to you by the OWL at Purdue University. When printing this page, you must include the entire legal notice.

Copyright ©1995-2018 by The Writing Lab & The OWL at Purdue and Purdue University. All rights reserved. This material may not be published, reproduced, broadcast, rewritten, or redistributed without permission. Use of this site constitutes acceptance of our terms and conditions of fair use.

The Research Paper

There will come a time in most students' careers when they are assigned a research paper. Such an assignment often creates a great deal of unneeded anxiety in the student, which may result in procrastination and a feeling of confusion and inadequacy. This anxiety frequently stems from the fact that many students are unfamiliar and inexperienced with this genre of writing. Never fear—inexperience and unfamiliarity are situations you can change through practice! Writing a research paper is an essential aspect of academics and should not be avoided on account of one's anxiety. In fact, the process of writing a research paper can be one of the more rewarding experiences one may encounter in academics. What is more, many students will continue to do research throughout their careers, which is one of the reasons this topic is so important.

Becoming an experienced researcher and writer in any field or discipline takes a great deal of practice. There are few individuals for whom this process comes naturally. Remember, even the most seasoned academic veterans have had to learn how to write a research paper at some point in their career. Therefore, with diligence, organization, practice, a willingness to learn (and to make mistakes!), and, perhaps most important of all, patience, students will find that they can achieve great things through their research and writing.

The pages in this section cover the following topic areas related to the process of writing a research paper:

• Genre - This section will provide an overview for understanding the difference between an analytical and argumentative research paper.
• Choosing a Topic - This section will guide the student through the process of choosing topics, whether the topic be one that is assigned or one that the student chooses themselves.
• Identifying an Audience - This section will help the student understand the often times confusing topic of audience by offering some basic guidelines for the process.
• Where Do I Begin - This section concludes the handout by offering several links to resources at Purdue, and also provides an overview of the final stages of writing a research paper.

How to Write a Research Paper (+ Free AI Research Paper Writer)

Table of contents

Meredith Sell

Over the years, I've managed to vastly improve how I write research papers.

The three major game-changers for me, in terms of quality of the finished piece, have been:

• Following the research paper checklist (see below)
• Developing the thesis before starting to write
• And, more recently, using AI to improve my research paper draft

Let's break down each of these elements and produce the kind of research papers that get cited in magazines.

FREE AI research paper writer > FREE AI research paper writer >

What is a research paper, and how is it written differently?

Research papers are longer and more in-depth than essays. They require extensive research and evidence-based arguments. Research papers also typically have a more formal structure and require citations and references.When academics want to find a balanced and comprehensive view on a given topic, they usually seek a research paper.

Like most writing assignments, a research paper can be broken down into simple steps. Research papers follow the same basic writing process as explanatory or persuasive essays — but instead of making an argument or drawing greater meaning from the topic, the research paper is primarily concerned with concrete facts that may be analyzed, examined, or interpreted to better understand the paper’s central topic.

This is good news if you enjoy research: you’ll be doing a lot of it. The ultimate quality of your paper depends on you conducting thorough, complete research — and relying on reputable sources.

How to Properly Write a Research Paper Using AI

1. make a checklist based on the assignment description, and fill it out with ai.

Your professor has likely specified some criteria for your research paper:

• Length (in pages or words)
• Type of topic (the War of 1812, ancient Greece, agriculture, etc.)
• Elements that must be included, such as analysis, discussion, and comparison.
• Types of sources you must draw from (academic papers, encyclopedias, etc.)
• Source attribution style
• Formatting style

Go through the assignment description and create a checklist of those criteria. You can use this checklist throughout the research and writing process as well:

AI can really help you get some traction with your research paper in the preperation stage. This includes two main steps:

• Brainstorming paper topic idea
• Outlining based on your topic, basing the prompt on the assignment

2. Choose a topic you’re curious about, or use AI to help you with that

A sure way to write a boring research paper is to pick a topic you have no interest in, like summer temperatures in the desert or the life cycle of a flea. (Though someone’s probably interested in those things.)

Instead, follow your curiosity.

If your paper is for a writing class, you may have a lot of freedom to choose what you write about, so tap into your interests. Are you intrigued by the history of roller skating or the invention of the soccer cleat? Or how teen social dynamics have changed with evolving technology (think: home phones → online instant messaging → flip phones → smartphones)?

If you’re writing for a class in a subject like history, art, or science, you’ll probably have more restrictions on what you can write about — like a time period or type of art or science — but you can still use your curiosity to pick an interesting topic.

If you’re having a tough time, try brainstorming a list of things you’ve wondered about. Ask “ what’s up with… ” and see what comes to mind.

For example:

What’s up with traffic circles and why are they supposedly better for traffic patterns than a light or four-way stop?

What’s up with country music sounding more and more like hip-hop?

What’s up with people who have gluten allergies being able to eat bread in Europe but not the US?

Once you have a list, choose the topic you find most interesting (and appropriate for the assignment).

If your mind draws a blank, you can utilize AI to help you choose a topic. Let's say your course is about mid century art. You can go to a tool like Wotdtune and ask it to give you ideas for creative mid century art essays. See example below.

3. Develop your thesis (and guide your research) by asking a research question

Even though a research paper may not necessarily take a side on a topic, it still needs a thesis, aka a central idea or focus that drives the piece from beginning to end. 

We wrote a whole guide on writing thesis statements , so here we’ll just give you this tip:

Use a research question to develop your thesis

A research question is a variation on the “What’s up with…” questions from the last tip — but it will zoom in more specifically on the aspect of your topic that you’re investigating.

Why were the Irish so dependent on potatoes?

Did any women in ancient Greece enjoy relative freedom and autonomy?

You may already know the answer to these questions, or you may not. Either way, they give you a place to start in your research. Once you have your question, set out to:

• Find the initial answer.
• Gather more context (the who, what, when, where, why, how) around that answer.
• Revise your research question and turn it into your thesis.

This process helps tighten your focus from a broad topic that could fill books to a specific angle that can be meaningfully explored in the few pages of your paper.

Instead of the potato famine , write about why England was to blame for the potato famine’s devastating effects on the Irish.

Instead of ancient Greece or women in ancient Greece , write about how Spartan women’s lives differed from the lives of women in Athens.

4. Skim sources and use AI to perform research for your paper

Your research question can help you quickly determine whether information is relevant to your paper. As you gather initial sources, skim them — and then use your research question to decide whether to keep or discard the source. 

Does the source cover information relevant to my research question?

Yes: Keep to read later.

No: Discard and move on to the next source.

This approach will save you precious research time. You won’t waste limited hours reading sources that don’t have a single helpful fact.

If skimming is hard for you (as a deep reader, I get it), Wordtune can help. Paste the link to your online source, upload a scanned PDF, or copy the text, and the tool will scan and summarize for you. You can always come back later and closely read the most useful sources.

5. Make note of the most interesting facts you find

Along with taking detailed notes of your research (complete with all the source info you need to make proper citations), highlight the most interesting facts you come across. You could stick these in a section together or mark them in a way that makes them stand out.

Why should you do this?

Because later on, one of these fascinating factoids could have a direct connection to your thesis — and make a great hook for the start of your paper. Instead of digging through all of your notes to try to remember what that interesting tidbit was, you’ll be able to find it easily.

6. Organize your research

There are plenty of ways to organize your notes, but I suggest breaking them up into subtopics and categories.

• Subtopic: A topic related to your main topic or thesis that needs to be explained and understood by readers in order to understand your main topic or thesis. For example: Land ownership in Ireland under British rule.
• Category: An overarching concept that several subtopics fall under. For example: British restrictions on the Irish.

To start, I would focus on the subtopics and then group them into categories.

As you organize, use the formatting tools in your word processor to tag headings and subheadings. For example, all categories would be an H2 (Heading 2), while all subtopics would be an H3 (Heading 3). 

Tagging your categories and subtopics this way will help you develop your outline. Just organize your categories and subtopics in a logical order, and you’ll have a skeleton of an outline ready to go.

7. Write with your research document open

No one can remember everything they found while researching — you’ll need to reference your research document throughout the writing process. No question there.

But you can make this easier (and keep your writing process efficient) by:

Keeping your research document open and in clear view.

I like to put my draft document and my research document side by side on my screen, so I can see them both at the same time. 

Another approach would be to paste the information you need directly into your draft document — in the order you’ll need it. (Your outline will help you know what you need.)

8. Steal the TK trick from journalists

In the middle of drafting your paper, you find that you’re missing a fact. 

You neglected to write down how many Irish people starved due to the potato famine.

You don’t know what age Spartan women were able to own property.

Instead of derailing your writing and searching for that information, write the sentence you want to write and stick a “TK” where the missing fact should go.

“TK” stands for “to come” (don't ask us why) and is a placeholder used by journalists to mark missing information they’ll fill in later. Using TK allows you to keep writing without getting off track every time you discover your research didn’t cover everything.

A whopping TK Irish people starved, thanks to the combination of famine and British oppression.

At age TK , Spartan girls became women who were able to own property, a right that their sisters in Athens did not enjoy.

9. Revise, explain, paraphrase with AI as your research/writing assistant

Using the right researching tools can get you a lot way.

If you’re ever at a loss for words — writing clunky, clumsy sentences, struggling to explain a concept, or having a hard time paraphrasing a source — Wordtune can serve as your AI sidekick.  

Simply highlight the sentence in question and browse Wordtune’s suggestion for a better wording.

You can also use Wordtune Spices to come up with examples and counter arguments for whatever you're writing about or even find stats and facts, complete with source citations

Wordtune doesn’t do all of the writing for you, but it can help you sharpen your ideas on the sentence level, so you can hand in a research paper with good writing that’s still very much your own.

Share This Article:

How to Craft Your Ideal Thesis Research Topic

How to Craft an Engaging Elevator Pitch that Gets Results

Eight Steps to Craft an Irresistible LinkedIn Profile

Looking for fresh content, thank you your submission has been received.

Hire a Research Paper Writer for Your Writing Projects

Browse 10,125 research paper writers online, hire skilled freelance research paper writing freelancers on guru and get work done on a flexible and secure platform.

$250 Million

• 100% Customer Satisfaction Rate Based on 2 reviews

Top Research Paper Writers

• Research Paper Writer

New Delhi, Delhi, India

• Research Papers
• Article Writing
• Blog Writing
• Content Writing
• Copywriting
• Energy Management
• Healthcare Consulting

Content Writing |Copywriter | Blogs

Top Guru Assistants content strategist with 12+ years of industry experience, We create personalized content roadmaps for clients across the board. Writing content and social media that enhances the visibility of any brand and helps them position themselves in the best possible way is our forte. A passionate health and wellness writer too, we have now added writing well-researched articles on medical cannabis/marijuana to our arsenal. Understanding your business/product/service and what you wish... View more

Lahore, Punjab, Pakistan

• Biography Writing
• Book Editing
• Book Proposals
• Book Writing
• Business Books
• Childrens Book Writing
• Cookbook Writing
• eBook Writing

White Papers

About this gig Let me write your white paper for you. My work is always original. I never plagiarize or recycle projects. I will select new, peer-reviewed scientific journal articles for your paper and include all cited work in the references page. All work will be in APA format, Times New Roman, size 12 font. I am a doctoral candidate and have a ton of experience in writing research papers. Although my major is in public health/epidemiology, I can write a paper for you on almost any subject. Pl... View more

Dera Ghazi Khan, Punjab, Pakistan

About this gig Do You want to Simple, Amazing, Professional, Corporate, Business Catalog and White Paper STOP SEARCHING..! You have come to the right place.. Packages Provided: Layout Design for Cover and Pages, with PDF output. Please be guided by package pricing.  Why trust me? and what benefits you will get? Less than 1 Hour Response Time Premium Quality and 100% Satisfaction guaranteed If you have brand guideline, we will use it perfectly Swift and Reliable Communication Use of Relevant phot... View more

Multan, Punjab, Pakistan

• Paper Writing
• Research Article
• Research Projects
• Academic Editing
• Academic Essays
• Academic Research
• Academic Writing

Academic writing

As an accomplished academic writer, I offer a comprehensive range of writing services tailored to meet the diverse needs of clients in the academic realm. My expertise spans various disciplines, including but not limited to humanities, social sciences, natural sciences, and engineering. KEY SKILLS: Proficient in conducting extensive research and analysis to develop well-structured and insightful academic papers. Adept at adhering to various citation styles, such as APA, MLA, Chicago, and Harvard... View more

Nairobi, Nairobi, Kenya

• Annotated Bibliography
• Research Paper
• Academic Writing & Research

APA and MLA Research Papers

I deliver original, articulate and high-quality APA, MLA Research Papers in the following desciplines: Business I.T Environmental Science Pharmacy Medicine Literature Human resource Management Economics Psychology Sociology History Nursing Political science, Law and Criminology etc I will also deliver on-point articles, blogs, and articles View more

Faisalabad, Punjab, Pakistan

• Research Articles
• Art Research
• Article Editing
• Article Proofreading
• Behavioral Research
• Communication Skills

Creative, Content and Technical Writing

Professional Research, Article and Technical Writer            My goal is to create high-level writing content. I am on the way to achieve my goal.  I am experienced in the following fields: -  1. Digital Marketer                           2. Facebook Marketing                                              3. Research Writing  4. Blog Post Writer                           5. Article Writing                                                    6. Internet Research         7. Content Writing         ... View more

Jatoi, Punjab, Pakistan

• Research Writing
• Research Paper Writing
• Creative Writing

Thesis, Reports & Research Paper Writing

Writing the research is not so easy but don''t worry, i''ll do. i am experienced research paper, thesis and research based writing freelancer since 2010. I have practical hands on it and did lot of researches before writing. I offer plagiarism free research writing. You can find my research based writing stuff samples including thesis, papers, reports, articles, blogs and essays in my portfolio. i''ll offer negotiable services depending on work time limit, quantity and quality. I am available for ... View more

Karachi, Sindh, Pakistan

• Arabic Language
• Data Entry Typing
• Essay Writing
• Public Relations Management

writing research,articles and essays

I am a writer who can write research papers, articles,essays,social media posts,websites articles as best as possible in Arabic and Urdu. I have most experience in this field and completed a lot of projects at many platforms of freelancing. Author of two book. In the result of above mentioned skills achieved experience in data entry and typing. View more

Rawalpindi, Punjab, Pakistan

• Educational Writing
• Report Writer
• Report Writing

Research Reports & Essays

?Expert Researcher and Writer for Essays, Reports, Papers and Articles? Got a deadline breathing down your neck? Need a killer research report, essay, paper, case study, or article pronto? You''re in the right spot! I''m geared up to be your go-to research and writing guru. I''ll dive into the details, gather info with precision, and whip up polished essays, reports, papers, or articles crafted exclusively for your needs. Throughout my career, I have compiled various essays, reports, papers, and ar... View more

Rawalpindi, Sindh, Pakistan

• Academic Content Writing
• Analytical Writing

Academic Research Writing

With expertise in writing well-research articles in the domains of Social Sciences, I have equipped myself with the vast knowledge of International Relations, US history, World Politics and Diplomacy. If you seek quick help in such domains of Social Sciences, you have reached a perfect gig. My expertise includes (with no limits to): International Relations: Theories of IR ("isms") and International Law Political Science: Governments, Political Systems, Political Ideology, the Big Game, Political... View more

Dhaka, Dhaka, Bangladesh

• Engineering (Mechanical / Chemical / Civil / Electrical)
• Literature Review
• Mechanical Engineering
• Proposal Writing

Good day, I have completed my own research paper previously about " Renewable energy". Now, I think I will help people out there to help them to write their own research papers. # Educational background:- B.Sc. in Mechanical Engineering. # Previously done:- Paper on renewable energy. (I am uploading it on portfolio) #Service I am offering: Table of content creation # I will help you to find out a suitable topic to have a go. ## Most importantly I have a good precise and concise hand on some si... View more

• Academic Consulting
• Assignment Writing

Research Paper and Academic Writing

Hi, I am providing assignment writing, research paper writing, research article writing and all kinds of academic writing services. Kind Regards View more

Varanasi, Uttar Pradesh, India

• Scientific Research
• Scientific Writing

Research Paper Writing and editing

I've written an edited several research papers and book chapters and know how to get it done. I can do the writing work based on the given references and results. I've been there and know how tedious it gets to the writing and referencing after going through the turmoil of finding the desired results conclusions. I can help you get the writing work done in a short duration while you can focus on your research or other things. View more

As a professional research writer, I possess the skills and expertise to conduct thorough research and produce high-quality written content that effectively communicates research findings. With experience in various research methods and techniques, I am capable of delivering insightful reports, academic papers, and other research-based content that meets the specific needs of my clients. I am committed to upholding ethical and legal standards, and I take pride in presenting my work in a clear, c... View more

Bahawalpur, Punjab, Pakistan

• Research Report
• Academic Papers

Research, Case-study & Reports writing

Hi, I''m Abdullah. I am an experienced writer with 7 years of experience. I have been writing research-based content for many clients in the across the globe. I am having experience in writing research reports, thesis, essays, case studies and proposals.  I have been providing 100% plagiarism-free and original research-based content for my clients. I will handle topics in different domains including, organisational behaviour, business ethics, human resources, economics, finance, accounting, psych... View more

Giza, Al Jizah, Egypt

• Academic Paper

Research paper writing

Are you in search of a skilled and reliable freelance writer to elevate your research paper projects to new heights? Look no further! I offer a comprehensive freelance research paper writing service tailored to meet the diverse needs of clients across academia, business, and beyond. What Sets My Service Apart: Expertise and Specialization: With a background in [insert your area of expertise or relevant qualifications], I bring a wealth of knowledge and expertise to every project. Whether you req... View more

Jhang Sadar, Punjab, Pakistan

• Research Writer
• Multicultural Education
• Netnography
• Qualitative Research
• Review Articles

Qualitative Research Writer

I will write a hundred percent original document (be it an research project, research writing, netnography social media research, review of articles ) that has been effectively accurate.  I have well experience of doing anthropological research writings. I have done multiple research projects based on villages, shrines and madrasahs as you can see my portfolio. I am willing to do work on any topic that is needed to be cover. If you need any services related to it, feel free to contact me. View more

Islamabad, Islamabad, Pakistan

• Academic Writing And Research

If you want help in academic writing. I’ll be there for you and write 100% unique and well-researched content for you. List of services Essay writing Research paper Educational blog post Assignments Report Writing prompt Proofreading and Editing Please feel free to contact me for detailed discussion about your project. View more

Academic Writer / Research Analyst

Hi, I am a Professional Academic writer. I have long experience in academic writing.  I am here to help you because... Sometimes writing an assignment, essay, thesis, Research paper, course work or a final year project can be stressful but with this online opportunity you can solve your problem. I will write a perfect assignment or research paper for you that will give you excellent grades/marks.    Areas of Expertise : International Relations Current Affairs Social Sciences Economics History Ge... View more

Sahiwal, Punjab, Pakistan

Research Documents on Solar Energy

Hi there! I am a EE graduate from NUST with majors in Solar Energy. I have over 3 years of experience in writing technical and academic works in renewable energy, especially Solar. I always aim to provide my clients with the highest quality service in the time frame and budget of their choice. My documents have always featured the highest quality content with negligible plagiarism. I am open to customization of orders according to your requirements. Kindly message me for further details! :) View more

Want to get work done by experts?

Looking for freelancers with a specific skill.

Find Freelancers

How to Hire a Research Paper Writer

Research paper writing is a form of academic writing which details the outcomes of a research study. It is done as a part of scholarly research, course assignments and sample surveys. The goal of professional research paper writers is to describe how the research was carried out and report the findings of the research. Students, academicians and research organizations require research paper writers for hire to help them write professional research papers. They help in performing big data collation that is further used in research papers, pre-thesis drafts and theses. Conducting research takes a lot of effort, so outsourcing the task of writing a research paper can help you save a great amount of time.

You can get the best research paper writers who are specialized in your field of research. All you have to do is provide a short brief and share the materials and data pertaining to your research. If you want to keep your research data confidential, you can ask your writer to sign a non-disclosure agreement before proceeding with your project.

What Do Freelance Online Research Paper Writers Do?

Research paper writers thoroughly work on each and every aspect of your research. They go through your notes and data to gain insights about your research methodology. Typically, the best research paper writers start by writing an abstract which briefly explains the purpose of the research. The abstract is then followed by an introduction which provides some background information on the research.  A major part of the research paper is dedicated to writing about materials and methodology. The final section of a research paper presents the results and findings of data. Research specialists make sure that every reference is properly cited and that a bibliography section is present at the end of the research paper.

If you want to write a research paper or dissertation for reporting your research findings, you can consider research paper writers for hire on the top freelance marketplaces, like Guru. Before hiring an online research paper writer, you need to ensure that your freelancer has:

Good skills in scientific reporting and is familiar with the format and terminologies used in research papers and documents.

Capability to conduct a literature review and use credible sources of information for the same.

Ability to follow specific criteria set by universities or journal editorial committees for writing different sections and presenting diagrams, tables and charts.

Familiarity with different citation styles such as APA, MLA and Harvard.

Capability to follow a particular style for in-text citations as well as bibliography as specified by the client.

Qualifications of Freelance Research Paper Writers

It is ideal that your freelancer has:

Professional education and training in writing and communication, and knowledge of a particular scientific discipline.

Knowledge of credible sources of information such as peer-reviewed journal articles, government documents and global guidelines.

Strong command of the English language and knowledge of appropriate scientific terminology.

Extensive portfolio of several research papers and dissertations written for different clients.

Benefits of Hiring Freelance Research Paper Writers

Hire a research paper writer and get your work done:

You can hire a freelancer online for helping you compile all your research findings in a well-formatted document.

They can help you prepare flowcharts, process diagrams and relationship diagrams.

They can organize and compile your data in the form of tables, graphs and charts.

They can prepare accurate references and appendix sections pertaining to the specific requirements.

Post a job today and receive free quotes from research paper writers within hours.

Why over 3 million people choose us, credibility.

We verify Freelancers, publish their feedback scores and All-Time Transaction Data to help you identify time-tested professionals across the globe.

Flexibility

We provide multiple Payment terms and flexible Agreements to enable you to work the way you want.

We offer SafePay payment protection and your choice of preferred payment method for financial peace of mind.

We have the lowest fees in the industry, providing you with maximum value at minimum cost.

Our dedicated support team works 24/7 to resolve all of your queries over the phone or email, no matter where you are located.

Why Choose Guru

It's Easy to Get Work Done on Guru

Create your free job posting and start receiving Quotes within hours.

Hire Freelancers

Compare the Quotes you receive and hire the best freelance professionals for the job.

Get Work Done

Decide on how and when payments will be made and use WorkRooms to collaborate, communicate and track work.

Make Secure Payments

Choose from multiple payment methods with SafePay payment protection.

See How Guru Works

People Also Search For

• English Language Experts
• Creative Writers
• Academic Researchers
• Copywriters
• Report Writers
• Academic Editing Services
• Data Entry Experts
• Technical Writers
• Translators
• Microsoft Word Experts
• Essay Writers
• Book Writers
• Data Managers
• Management Experts
• Scientific Researchers
• Microsoft Developers
• Science Consultants

Browse Skills Related to Research Paper Writers

• Genealogy Researchers
• Transcriptionists
• Keyword Researchers
• Newsletters
• News Writers
• English Grammar Experts
• Journalists
• English Translators
• Web Content Writers
• Adobe InDesign Experts
• Short Story Writers
• Content Marketers
• Newspaper Writers
• Magazine Article Writing
• CMS (Content Management System) Experts
• Hindi Translators

Browse Top Freelancer Locations for Research Paper Writers

• Bhakkar, Pakistan
• Kolkata, India
• Islamabad, Pakistan
• Nairobi, Kenya
• Rawalpindi, Pakistan
• Multan, Pakistan
• Lagos, Nigeria
• Mumbai, India
• Chennai, India
• Bengaluru, India
• Lahore, Pakistan
• Karachi, Pakistan
• Dhaka, Bangladesh
• New Delhi, India
• Faisalabad, Pakistan

Find Freelancers by Category

• Programming & Development
• Design & Art
• Writing & Translation
• Administrative & Secretarial
• Sales & Marketing
• Business & Finance
• Engineering & Architecture
• Education & Training

Browse More on Guru

By Location

Your teaching and learning resource for helping students master academic writing.

750 First Street NE Washington, DC 20002 www.apa.org

Terms of Use | Privacy Statement ©2023 American Psychological Association. All Rights Reserved.

“How do I cite an Instagram post?”

How can academic writer help you, “how do i format an annotated bibliography”, “i need help ordering my headings in my paper.”.

Academic Writer is APA’s all-inclusive digital resource for:

• learning about the scholarly research and writing process,
• creating a formatted collection of references,
• writing papers and citing references in APA Style ® , and
• putting into practice the guidelines from the Publication Manual of the American Psychological Association (7th ed.).

“I’m a librarian or administrator looking to support institution-wide access”

“I’m a student looking for personal access to help write my papers”

Do these pain points sound familiar? Academic Writer is here to help.

Research Paper Writer

Ai-powered research paper writing tool.

• Academic Research: Write a research paper for your coursework, thesis, or dissertation.
• Professional Research: Create a well-structured report for your professional work, including market research, policy papers, or white papers.
• Personal Research: Draft a detailed essay on a topic of personal interest.
• Content Creation: Develop a long-form blog post or article based on in-depth research.

New & Trending Tools

Brand management tutor, lesson plan maker, marketing research tutor.

Home / Guides / Citation Guides / How to Cite Sources

How to Cite Sources

Here is a complete list for how to cite sources. Most of these guides present citation guidance and examples in MLA, APA, and Chicago.

If you’re looking for general information on MLA or APA citations , the EasyBib Writing Center was designed for you! It has articles on what’s needed in an MLA in-text citation , how to format an APA paper, what an MLA annotated bibliography is, making an MLA works cited page, and much more!

MLA Format Citation Examples

The Modern Language Association created the MLA Style, currently in its 9th edition, to provide researchers with guidelines for writing and documenting scholarly borrowings.  Most often used in the humanities, MLA style (or MLA format ) has been adopted and used by numerous other disciplines, in multiple parts of the world.

MLA provides standard rules to follow so that most research papers are formatted in a similar manner. This makes it easier for readers to comprehend the information. The MLA in-text citation guidelines, MLA works cited standards, and MLA annotated bibliography instructions provide scholars with the information they need to properly cite sources in their research papers, articles, and assignments.

• Book Chapter
• Conference Paper
• Documentary
• Encyclopedia
• Google Images
• Kindle Book
• Memorial Inscription
• Museum Exhibit
• Painting or Artwork
• PowerPoint Presentation
• Sheet Music
• Thesis or Dissertation
• YouTube Video

APA Format Citation Examples

The American Psychological Association created the APA citation style in 1929 as a way to help psychologists, anthropologists, and even business managers establish one common way to cite sources and present content.

APA is used when citing sources for academic articles such as journals, and is intended to help readers better comprehend content, and to avoid language bias wherever possible. The APA style (or APA format ) is now in its 7th edition, and provides citation style guides for virtually any type of resource.

Chicago Style Citation Examples

The Chicago/Turabian style of citing sources is generally used when citing sources for humanities papers, and is best known for its requirement that writers place bibliographic citations at the bottom of a page (in Chicago-format footnotes ) or at the end of a paper (endnotes).

The Turabian and Chicago citation styles are almost identical, but the Turabian style is geared towards student published papers such as theses and dissertations, while the Chicago style provides guidelines for all types of publications. This is why you’ll commonly see Chicago style and Turabian style presented together. The Chicago Manual of Style is currently in its 17th edition, and Turabian’s A Manual for Writers of Research Papers, Theses, and Dissertations is in its 8th edition.

Citing Specific Sources or Events

• Declaration of Independence
• Gettysburg Address
• Martin Luther King Jr. Speech
• President Obama’s Farewell Address
• President Trump’s Inauguration Speech
• White House Press Briefing

Additional FAQs

• Citing Archived Contributors
• Citing a Blog
• Citing a Book Chapter
• Citing a Source in a Foreign Language
• Citing an Image
• Citing a Song
• Citing Special Contributors
• Citing a Translated Article
• Citing a Tweet

6 Interesting Citation Facts

The world of citations may seem cut and dry, but there’s more to them than just specific capitalization rules, MLA in-text citations , and other formatting specifications. Citations have been helping researches document their sources for hundreds of years, and are a great way to learn more about a particular subject area.

Ever wonder what sets all the different styles apart, or how they came to be in the first place? Read on for some interesting facts about citations!

1. There are Over 7,000 Different Citation Styles

You may be familiar with MLA and APA citation styles, but there are actually thousands of citation styles used for all different academic disciplines all across the world. Deciding which one to use can be difficult, so be sure to ask you instructor which one you should be using for your next paper.

2. Some Citation Styles are Named After People

While a majority of citation styles are named for the specific organizations that publish them (i.e. APA is published by the American Psychological Association, and MLA format is named for the Modern Language Association), some are actually named after individuals. The most well-known example of this is perhaps Turabian style, named for Kate L. Turabian, an American educator and writer. She developed this style as a condensed version of the Chicago Manual of Style in order to present a more concise set of rules to students.

3. There are Some Really Specific and Uniquely Named Citation Styles

How specific can citation styles get? The answer is very. For example, the “Flavour and Fragrance Journal” style is based on a bimonthly, peer-reviewed scientific journal published since 1985 by John Wiley & Sons. It publishes original research articles, reviews and special reports on all aspects of flavor and fragrance. Another example is “Nordic Pulp and Paper Research,” a style used by an international scientific magazine covering science and technology for the areas of wood or bio-mass constituents.

4. More citations were created on  EasyBib.com  in the first quarter of 2018 than there are people in California.

The US Census Bureau estimates that approximately 39.5 million people live in the state of California. Meanwhile, about 43 million citations were made on EasyBib from January to March of 2018. That’s a lot of citations.

5. “Citations” is a Word With a Long History

The word “citations” can be traced back literally thousands of years to the Latin word “citare” meaning “to summon, urge, call; put in sudden motion, call forward; rouse, excite.” The word then took on its more modern meaning and relevance to writing papers in the 1600s, where it became known as the “act of citing or quoting a passage from a book, etc.”

6. Citation Styles are Always Changing

The concept of citations always stays the same. It is a means of preventing plagiarism and demonstrating where you relied on outside sources. The specific style rules, however, can and do change regularly. For example, in 2018 alone, 46 new citation styles were introduced , and 106 updates were made to exiting styles. At EasyBib, we are always on the lookout for ways to improve our styles and opportunities to add new ones to our list.

Why Citations Matter

Here are the ways accurate citations can help your students achieve academic success, and how you can answer the dreaded question, “why should I cite my sources?”

They Give Credit to the Right People

Citing their sources makes sure that the reader can differentiate the student’s original thoughts from those of other researchers. Not only does this make sure that the sources they use receive proper credit for their work, it ensures that the student receives deserved recognition for their unique contributions to the topic. Whether the student is citing in MLA format , APA format , or any other style, citations serve as a natural way to place a student’s work in the broader context of the subject area, and serve as an easy way to gauge their commitment to the project.

They Provide Hard Evidence of Ideas

Having many citations from a wide variety of sources related to their idea means that the student is working on a well-researched and respected subject. Citing sources that back up their claim creates room for fact-checking and further research . And, if they can cite a few sources that have the converse opinion or idea, and then demonstrate to the reader why they believe that that viewpoint is wrong by again citing credible sources, the student is well on their way to winning over the reader and cementing their point of view.

They Promote Originality and Prevent Plagiarism

The point of research projects is not to regurgitate information that can already be found elsewhere. We have Google for that! What the student’s project should aim to do is promote an original idea or a spin on an existing idea, and use reliable sources to promote that idea. Copying or directly referencing a source without proper citation can lead to not only a poor grade, but accusations of academic dishonesty. By citing their sources regularly and accurately, students can easily avoid the trap of plagiarism , and promote further research on their topic.

They Create Better Researchers

By researching sources to back up and promote their ideas, students are becoming better researchers without even knowing it! Each time a new source is read or researched, the student is becoming more engaged with the project and is developing a deeper understanding of the subject area. Proper citations demonstrate a breadth of the student’s reading and dedication to the project itself. By creating citations, students are compelled to make connections between their sources and discern research patterns. Each time they complete this process, they are helping themselves become better researchers and writers overall.

When is the Right Time to Start Making Citations?

Make in-text/parenthetical citations as you need them.

As you are writing your paper, be sure to include references within the text that correspond with references in a works cited or bibliography. These are usually called in-text citations or parenthetical citations in MLA and APA formats. The most effective time to complete these is directly after you have made your reference to another source. For instance, after writing the line from Charles Dickens’ A Tale of Two Cities : “It was the best of times, it was the worst of times…,” you would include a citation like this (depending on your chosen citation style):

(Dickens 11).

This signals to the reader that you have referenced an outside source. What’s great about this system is that the in-text citations serve as a natural list for all of the citations you have made in your paper, which will make completing the works cited page a whole lot easier. After you are done writing, all that will be left for you to do is scan your paper for these references, and then build a works cited page that includes a citation for each one.

Need help creating an MLA works cited page ? Try the MLA format generator on EasyBib.com! We also have a guide on how to format an APA reference page .

2. Understand the General Formatting Rules of Your Citation Style Before You Start Writing

While reading up on paper formatting may not sound exciting, being aware of how your paper should look early on in the paper writing process is super important. Citation styles can dictate more than just the appearance of the citations themselves, but rather can impact the layout of your paper as a whole, with specific guidelines concerning margin width, title treatment, and even font size and spacing. Knowing how to organize your paper before you start writing will ensure that you do not receive a low grade for something as trivial as forgetting a hanging indent.

Don’t know where to start? Here’s a formatting guide on APA format .

3. Double-check All of Your Outside Sources for Relevance and Trustworthiness First

Collecting outside sources that support your research and specific topic is a critical step in writing an effective paper. But before you run to the library and grab the first 20 books you can lay your hands on, keep in mind that selecting a source to include in your paper should not be taken lightly. Before you proceed with using it to backup your ideas, run a quick Internet search for it and see if other scholars in your field have written about it as well. Check to see if there are book reviews about it or peer accolades. If you spot something that seems off to you, you may want to consider leaving it out of your work. Doing this before your start making citations can save you a ton of time in the long run.

Finished with your paper? It may be time to run it through a grammar and plagiarism checker , like the one offered by EasyBib Plus. If you’re just looking to brush up on the basics, our grammar guides  are ready anytime you are.

How useful was this post?

Click on a star to rate it!

We are sorry that this post was not useful for you!

Let us improve this post!

Tell us how we can improve this post?

Citation Basics

Harvard Referencing

Plagiarism Basics

Plagiarism Checker

Upload a paper to check for plagiarism against billions of sources and get advanced writing suggestions for clarity and style.

Get Started

• Writing Center
• Writing Resources
• Composition Seminar
• University Writing Seminar
• Student Writing Resources
• UWS Instructor Resources
• Instructor Resources
• Course Application for Instructors
• FAQ for Instructors
• FAQ for Students
• Index of Papers
• Library Research
• English Language Tutoring
• Nomination Form
• Administration
• Faculty and Instructors
• Degree Programs
• Majors and Minors
• Graduate Programs
• The Brandeis Core
• School of Arts and Sciences
• Brandeis Online
• Brandeis International Business School
• Graduate School of Arts and Sciences
• Heller School for Social Policy and Management
• Rabb School of Continuing Studies
• Precollege Programs
• Faculty and Researcher Directory
• Brandeis Library
• Academic Calendar
• Undergraduate Admissions
• Summer School
• Financial Aid
• Research that Matters
• Resources for Researchers
• Brandeis Researchers in the News
• Provost Research Grants
• Recent Awards
• Faculty Research
• Student Research
• Centers and Institutes
• Office of the Vice Provost for Research
• Office of the Provost
• Housing/Community Living
• Campus Calendar
• Student Engagement
• Clubs and Organizations
• Community Service
• Dean of Students Office
• Orientation
• Hiatt Career Center
• Spiritual Life
• Graduate Student Affairs
• Directory of Campus Contacts
• Division of Creative Arts
• Brandeis Arts Engagement
• Rose Art Museum
• Bernstein Festival of the Creative Arts
• Theater Arts Productions
• Brandeis Concert Series
• Public Sculpture at Brandeis
• Women's Studies Research Center
• Creative Arts Award
• Our Jewish Roots
• The Framework for the Future
• Mission and Diversity Statements
• Distinguished Faculty
• Nobel Prize 2017
• Notable Alumni
• Working at Brandeis
• Commencement
• Offices Directory
• Faculty & Staff
• Alumni & Friends
• Parents & Families
• 75th Anniversary
• Directories
• New Students
• Shuttle Schedules
• Support at Brandeis

University Writing Program

Unit 2 essay: topics in morality, research proposal.

Good research is driven by analytical questions. However, in order to know what questions to ask, it is necessary to learn what research already exists on your topic. What are the gaps in the literature? What conflicts exist? Why do these questions matter? How will you manage to insert yourself into the larger conversation on your topic?

Therefore, in preparation for the draft of the multi-source research paper, please prepare a research proposal. As noted on the syllabus, the research proposal is not graded for quality, but on completion. If you fully execute all requested components of the proposal, you will receive full credit (10% of the final grade).

Your proposal should include the following sections, preferably in this order:

Introduction to the project (~1 paragraph)

Provide an introduction to your chosen topic. Attempt to frame for the reader what you’re planning to explore and why this topic is interesting. There likely will not be a thesis yet, since your research will not be complete (but there could be a preliminary thesis).

Preliminary literature review (~1-2 pages)

Based on your preliminary foray into the literature, synthesize for the reader what you have learned about your topic. What does the initial literature seem to show? What questions are unanswered? What conflicts or contradictions exist in the literature (e.g., many cultures find infidelity to be immoral – though not all – but some evidence suggests humans are predisposed to cheat)? Don’t be afraid of complications – messiness is an opportunity to intervene. NOTE: you should be citing the literature at the sentence-level in this section.

Library research method (~1 page)

How will you research this topic? What types of searches will you want to do? What information will you seek out? What keywords might you use? Are you interested in exploring sources outside of the sciences? Don’t rush past this section – really consider your plan for your research.

Significance / motive (~1-2 paragraphs)

What do you hope to accomplish with your research? What is the larger motivation for exploring this topic? Why does the research matter? Think about why a reader might want to know about this topic.

Weekly timeline (~1/2 page)

In order to facilitate your research over the remainder of the semester, please come up with a week-by-week plan for how you will approach your research. What do you plan to do each week? Be specific.

March 22-28:                                  (Conferences this week)

March 29-April 4: April 5-11: April 11 – Draft due April 12-18:                                    (Conferences this week) April 19-25:                                    (Spring break this week) April 26-May 2: May 5 – Revision due

Annotated bibliography (minimum of 3-4 sources)

In addition to providing a list of the sources you have included thus far (in APA format), please include a sentence or two explaining how each source informs your research topic. For example: Lieberman, D., Tooby, J. and Cosmides, L. 2003. Does morality have a biological basis? An empirical test of the factors governing moral sentiments relating to incest. Proceedings of the Royal Society of London B 270: 819-826. This article shows how people have an aversion to sexual interactions with people that they grow up with. This argument conflicts with arguments that people avoid partners that look like themselves. Due: Thursday, March 21st, by 5 pm (via LATTE) 

Student quote: “I feel that this proposal was able to really ground my thoughts pertaining to what I want to do with this essay. Before writing it, I did not have a very good idea of the direction that I wanted to go in, but the proposal really allowed me to think about it in depth and generate ideas for the paper.”

Elissa Jacobs

• First-Year Writing
• Writing-Intensive Requirement
• J.V. Cunningham Awards

Data Management

D-Back  for iOS/Win/Mac - Data Recovery HOT

Recover Deleted Data from iOS/Win/Mac

Data Recovery

D-Back  Hard Drive Recovery - Hard Drive Data Recovery

Recover Deleted Data from PC/Mac

Windows/Mac Data Recovery

ChatsBack  for WhatsApp - WhatsApp Recovery

Recover Deleted WhatsApp Messages

WhatsApp Messages Recovery

ChatsBack  for LINE - LINE Recovery

Recover Deleted LINE Messages

LINE Messages Recovery

iMyTrans - Apps Data Transfer HOT

Transfer, Export, Backup, Restore WhatsApp Data with Ease

WhatsApp Data Transfer Tool

iTransor for LINE

Transfer, Export, Backup, Restore LINE Data with Ease

LINE Data Transfer Tool

Umate Pro  - Secure iOS Data Eraser

Permanently Erase iPhone/iPad/iPod Data to Secure your privacy

iPhone Data Eraser

AllDrive  - Multiple Cloud Storage Manager NEW

Manage All Cloud Drive Accounts in One Place

Multiple Cloud Storage Manager

AnyTo  - Location Changer HOT

Best iOS/Android Location Changer

iOS/Android Location Changer

MirrorTo  - Screen Mirror

Professional iOS/Android Screen Mirror

iOS/Android Screen Mirror

LockWiper  for iOS - iPhone Passcode Unlocker HOT

Remove iPhone/iPad/iPod touch Password

iPhone Passcode Unlocker

LockWiper  for Android - Android Passcode Unlocker

Unlock Android FRP Lock & All Screen Locks

Android Passcode Unlocker

Fixppo  for iOS - iPhone System Repair HOT

Fix your iPhone/iPad/iPod touch/Apple TV without losing data

iPhone System Repair Tool

iBypasser  - iCloud Activation Lock Bypasser

Bypass iCloud Activation Lock & Sim Lock

iCloud Activation Lock Bypasser

UltraRepair  - File Repair

Fix damaged and corrupted videos/photos/files/audio

Repair Corrupt Video/Photo/File

Passper  - Password Recovery Expert

Recover password for Excel/Word/PPT/PDF/RAR/ZIP/Windows

Office/Files/Windows Unlocker

FamiGuard  - Reliable Parental Control App

Remotely Monitor Your Kid's Device and Activity

Reliable Parental Control App

VoxNote  - AI Vocie Notes NEW

Transcribe real-time & recorded audio into text

Voice Notes with AI Summaries

Novi AI  - AI Story-to-Video Generator NEW

Convert Your Story & Novel to Original Video Easily

Convert Story & Novel to Video

RewriteX  - Al rewriter for anywhere NEW

Make Your Words Mistake-free And Clear

Mistake-free And Clear

EasifyAI  - Life-Changing AI Toolkit NEW

Innovative AI Toolbox to Take All The Heavy Lifting Off

Innovative AI Toolbox

LokShorts  - Locate best drama & short film NEW

Online Watching 1-minute Short Drama

Filme  - The Best Video Editor

Video Editor and Fast Slide Show Maker

MagicMic  - Real-Time Voice Changer HOT

Change Your Voice in Real-Time Easily

Real-Time Voice Changer

MarkGo  - Effective Watermark Remover

Manage Your Video & Image Watermark Easily

Effective Watermark Remover

V2Audio  - Video Convertor

Super Video Converter Makes Everything Easier

Super Video Converter

VoxBox - Ai Text-to-Speech Generator

Make Voiceover Easily with Cloning & TTS

Text-to-Speech Voice Generator

AnySmall  - Video Compressor NEW

One Click to Compress Videos While Keeping High Quality

One-click Video Compressor

TopClipper  - Video Downloader

Download Any Videos You Like from Any Platforms

Video Downloader from Any Platforms

TopMediai  - Online AI Tools Collection

Discover how AI Transforms Image & audio editing

Online AI Tools Collection

MagicPic  - AI Background Remover & Changer NEW

Remove and Change your Photo Background with Single Click

AI Background Remover & Changer

MusicAI  - AI Music Generator NEW

All-in-one generator to make AI songs

AI Music Generator

Productivity

ChatArt : Chatbot & AI Writer HOT

Generate AI Painting, Write AI Article and Marketing Copy Easily

Chatbot & AI Writer

ZoeAI  - Chat With Any PDF Document NEW

Start AI Conversation With PDF With One Click

The Best PDF AI Chat Assistant

FigCube  - Free Website Builder

Create A Blog Website Within Minutes

Free Website Builder

PromptWink  - AI Prompt Marketplace NEW

Get 1,000+ quality AI prompts from top prompt engineers

AI Prompt Marketplace

AI Tools : Complete Resource of AI Tools

Find The Exact AI Tool For Your Needs

AI Tools Navigation Page

iMyWork  - Personal AI Work Assistant App NEW

Provide professional work advise and support

AI Work Assistant

QRShow  - Professional QR Code Generator NEW

Create various static and dynamic QR codes for free

QR Code Generator

Support Center

Licenses, FAQs

Pre-Sales Inquiry, etc.

How-to Guides

Mobile/PC Issues Solutions

Product Center

iMyFone Products Free Trial

Writing Paper with AI Research Paper Writer

Category: AI Tools

May 30, 2024 6 mins read

A research paper shows how much aptitude you have related to the field. However, despite having the knowledge and experience on the subject, there might come a time when you get overwhelmed by organizing massive amounts of data and formatting it to the required standard.

With a dedicated AI paper writer, you can craft the exact type of content needed to get your superior's approval. Follow this post and understand how this technology and its natural language processing have made it easier to manage such a task.

In this article:

Part 1: What is AI Paper Writer

Part 2: hot ai paper writers list, part 3: writing paper with ai paper writer, part 4: more tips for a good research paper writing.

With an AI paper generator, you can create human-like unique essays and research papers by simply putting in your requirements and some essential details related to the topic.

As a student or a researcher, you might feel pressured when it comes to meeting paper deadlines. Utilizing an AI writing tool for assistance can greatly help streamline the execution of tasks, thereby saving a lot of time.

Most of these paper-writing AI tools can generate entire essays from scratch. Moreover, you can build a unique outline and get suggestions on relevant topics.

In addition, if you already have managed a paper, then you can paste the text and ask this tool to point out grammatical mistakes. Besides, these services can provide references and citations for the information sources used in the generated content, ensuring authentic and verifiable content.

When it comes to looking at the best AI paper writers, here are our few top picks. We will go over the functions and prices of each one for a quick comparison.

ChatArt is among the most useful and user-friendly AI writing platforms available. You can generate text using the AI Chat feature or utilize dedicated essay or article writing features to craft the research paper in your desired format and tone.

Moreover, you can fix grammatical errors and adjust an already-written academic paper using ChatArt's AI Editor tool.

Start your paper writing with the free AI Research Paper Writer with guidance .

• Engage in real-time Q&A with AI and obtain quick and accurate answers.
• Select different text creation modules according to scenario needs.
• Generate chat scripts, ad copy, novel, poetry, blogs, work reports, dream analysis, etc.
• Save valuable content via bookmarking for easy future access and use.

Here are some of its basic functionalities:

• It is an all-in-one writing assistant that generates content, translates to suitable language , and even polishes the writing.
• With the AI Chat tool, you can have real-time conversations for immediate solutions to queries.

Price: It offers a free plan along with cost-effective paid packages starting at $1 per month.

Jasper is one of the pioneers of AI generative writing. Initially, it offered to do copywriting but evolved into a complete article and research paper writing platform.

Some of its prominent functions are as follows:

• You can create high-quality and valuable content based on your requirements.
• The AI chat feature delivers error-free content.
• You can receive ideas on how to improve your research paper using Jasper.

Price: Jasper offers a 7-day free trial. Its paid plan begins at $39 per month.

This service is aimed at small businesses, but students and scholars can utilize its features to manage their research paper writing requirements.

Its functions include the following:

• You can manage the content in multiple tones, including sarcastic, joyful, positive, etc.
• It offers a built-in function to detect plagiarism.

Price: There is a free version available with paid plans beginning from $29 per month.

Writing papers with an AI writer is not a complicated science and can be easily done. However, it is pertinent that one chooses the right AI paper writer. This is why we recommend ChatArt. Its advanced AI capabilities can help you upgrade your writing skills. Moreover, it is reliable, which shows that it is trusted by more than 2 million writers.

In addition, you can first build a paper outline by giving the AI service a clear prompt. As the outline is provided to this AI research paper writer, you can accelerate the writing or simply ask ChatArt to craft an entire paper with accurate and structured content. Not only this, but this content is also well-researched and can be easily verified.

Here is what needs to be done to get started with ChatArt.

Enhance the efficiency and quality of your freelance content writing with Article Generator:

Step 1: Navigate to Article Generator in ChatArt.

Step 2: Input the topic of your freelance writing order.

The more details you give in the topic section; the better content writing result you will get.

Step 3: Select the country that the article aims at and click Generate Keywords . Select keywords based on the relevance, trends, and difficulty in the list.

If your customer provides the keywords, click the button named Already have keywords? Enter them here.

Step 4: Choose a desired type of passage content and click Generate for outline creation. You can modify, add, and remove any part of the outline before processing to the next step.

Step 5: Output language, article tone, and word count can be customized. You can make the options based on your need. Finally, click Generate to get the article.

Step 6: Select any words, sentences, or paragraphs in the output content that you want to raise questions about, generate pictures, optimize tone and length, and translate into another language.

Through the question function, you will be inspired by some unique perspectives.

Get more details about the strange topic of the order with AI Chat in ChatArt:

For example, you receive an order about the medical aspect. Here we go:

Step 1: Turn on the AI Chat function in ChatArt.

Step 2: Input your prompt like "I want more information about (the topic)" and send.

Step 3: You will get the required information. Besides, promoting under the given information can help you brainstorm on this topic.

With a little bit of effort, you can improve the quality of the research papers and convert them into top-notch written pieces.

Here are some more tips for writing a good research paper with the help of an AI paper generator.

1. Make a checklist of the criteria set out by an authority for your research paper. Consider the length, type of topic, elements that need to be included, types of sources to be used, and formatting style.

2. If unsure about the topic, get help from the AI paper generator.

3. Skim through different sources provided by the AI paper writer and perform the required research.

4. Make notes of the most interesting and relevant findings.

5. Organize the entire research and now write your paper.

6. If you find the paper difficult, ask the AI research paper writer to produce the entire essay.

7. Do not forget to revise and recheck.

As AI becomes increasingly advanced every day, research has also become very convenient for researchers and students. As long as the right AI paper writing tool , such as ChatArt, has been selected, you have nothing to worry about!

to Get More AI News & Tips

Philip Cevich

(Click to rate this post)

Generally rated 4.9 ( 256 participated)

Rated successfully!

You have already rated this article, please do not repeat scoring!

Home > AI Tools > Writing Paper with AI Research Paper Writer

• Artificial Intelligence /

Perplexity will research and write reports

A new feature called pages will do the searching, writing, and laying out of a report with just a prompt..

By Emilia David , a reporter who covers AI. Prior to joining The Verge, she covered the intersection between technology, finance, and the economy.

Share this story

AI search platform Perplexity is launching a new feature called Pages that will generate a customizable webpage based on user prompts. The new feature feels like a one-stop shop for making a school report since Perplexity does the research and writing for you.

Pages taps Perplexity’s AI search models to find information and then creates what I can loosely call a research presentation that can be published and shared with others.  In a blog post , Perplexity says it designed Pages to help educators, researchers, and “hobbyists” share their knowledge.

Users type out what their report is about or what they want to know in the prompt box. They can gear the writing more toward beginners, expert readers, or a more general audience. Perplexity searches for information, then begins writing the page by breaking down the information into sections, citing some sources, and then adding visuals. Users can make the page as detailed or concise as they want, and they can also change the images Perplexity uses. However, you can’t edit the text it generates; you have to write another prompt to fix any mistakes.

I tried out Pages ahead of time to see how it works. Pages is not geared toward people like me who already have an avenue to share our knowledge. But it doesn’t seem geared toward researchers or teachers, either. I wanted to see how it can break down complex topics and if it can help with the difficult task of presenting dense information to different audiences.

Among other topics, I asked Perplexity’s Pages to generate a page on the “convergence of quantum computing and artificial intelligence and its impact on society” across the three audience types. The main difference between audiences seems to be the jargon in the written text and the kind of website it takes data from. Each generated report pulls from different sources, including introductory blog posts like this one from IBM . It also cited Wikipedia, which drove the student report vibe home.

The Perplexity-generated page did a passable job of explaining the basics of quantum computing and how AI fits into the technology. But the “research” didn’t go as deep as I could have if I were writing the presentation myself. The more advanced version didn’t even really talk about “the convergence of quantum computing and AI.” It found blog posts talking about quantum inflection points , which is when quantum technologies become more commercially viable and is not at all related to what I asked it to write about.

Then, I asked Pages to write a report about myself, mainly because the information there is easily verifiable. But it only took information from my personal website and an article about me on my high school’s website — not from other public, easily accessible sources like my author page on The Verge . It also sometimes elaborated on things that had nothing to do with me. For example, I began my journalism career during the 2008 financial crisis. Instead of talking about the pieces I wrote about mass layoffs, Perplexity explained the beginnings of the financial crisis.

Pages does the surface-level googling and writing for you, but it isn’t research. Perplexity claims that Pages will help educators develop “comprehensive” study guides for students and researchers to create detailed reports on their findings. I could not upload a research paper for it to summarize, and I couldn’t edit the text it generated, two things I believe users who want to make the most of Pages would appreciate.

I do see one potential user for Pages, and it isn’t one Perplexity called out: students rushing to put out an assignment. Pages may improve in the future. Right now, it’s a way to get easy, possibly correct surface-level information into a presentation that doesn’t really teach anything.

Pages will be available to all Perplexity users, and the company says it’s slowly rolling it out to its free, Pro, and Enterprise users. 

Google Zero is here — now what?

Godzilla minus one gets a surprise netflix release, massive ticketmaster, santander data breaches linked to snowflake cloud storage, all of microsoft’s macbook air-beating benchmarks, netflix’s mike tyson vs. jake paul fight is postponed.

More from Artificial Intelligence

Alexa’s Fire TV search has a new AI, but it needs some work

Anthropic’s AI now lets you create bots to work for you

Custom GPTs open for free ChatGPT users

• Share full article

Advertisement

Supported by

Guest Essay

A Chill Has Fallen Over Jews in Publishing

By James Kirchick

Mr. Kirchick is a contributing writer to Tablet magazine, a writer at large for Air Mail and the author of “Secret City: The Hidden History of Gay Washington.”

This month, an account on X with the handle @moyurireads and 360 followers published a link to a color-coded spreadsheet classifying nearly 200 writers according to their views on the “genocide” in Gaza. Titled “Is Your Fav Author a Zionist?,” it reads like a cross between Tiger Beat and “The Protocols of the Elders of Zion.”

The novelist Emily St. John Mandel, the author of “Station Eleven” and “Sea of Tranquility,” earned a red “pro-Israel/Zionist” classification because, according to the list’s creator, she “travels to Israel frequently talks favorably about it.” Simply for posting a link to the Israeli chapter of the Red Cross, the novelist Kristin Hannah was deemed a “Zionist,” as was the author Gabrielle Zevin for delivering a book talk to Hadassah, a Jewish women’s organization. Needless to say, the creator of the list — whose post on X announcing it garnered over a million views within a few days — encourages readers to boycott any works produced by “Zionists.”

The spreadsheet is but the crudest example of the virulently anti-Israel — and increasingly antisemitic — sentiment that has been coursing through the literary world since the Hamas massacre of Oct. 7. Much of it revolves around the charge of genocide and seeks to punish Zionists and anyone else who refuses to explicitly denounce the Jewish state for allegedly committing said crime. Since a large majority of American Jews (80 percent of whom, according to a 2020 poll , said that caring about Israel is an important or essential part of their Judaism) are Zionists, to accuse all Zionists of complicity in genocide is to anathematize a core component of Jewish identity.

Over the past several months, a litmus test has emerged across wide swaths of the literary world effectively excluding Jews from full participation unless they denounce Israel. This phenomenon has been unfolding in progressive spaces (academia, politics, cultural organizations) for quite some time. That it has now hit the rarefied, highbrow realm of publishing — where Jewish Americans have made enormous contributions and the vitality of which depends on intellectual pluralism and free expression — is particularly alarming.

As is always and everywhere the case, this growing antisemitism is concomitant with a rising illiberalism. Rarely, if ever, do writers express unanimity on a contentious political issue. We’re a naturally argumentative bunch who — at least in theory — answer only to our own consciences.

To compel them to express support or disapproval for a cause is one of the cruelest things a society can do to writers, whose role is to tell society what they believe, regardless of how popular the message may be. The drawing up of lists, in particular, is a tactic with a long and ignominious history, employed by the enemies of literature — and liberty — on both the left and the right. But the problem goes much deeper than a tyro blacklist targeting “Zionists.”

One of the greatest mass delusions of the 21st century is the belief that Israel is committing a genocide against Palestinians. This grotesque moral inversion — in which a genocidal terrorist organization that instigated a war with Israel by committing the largest massacre of Jews since the Holocaust is absolved of responsibility while the victim of Hamas’s attack is charged with perpetrating the worst crime known to man — began taking shape before Israel even launched its ground invasion of Gaza.

A charitable description of those imputing genocidal motivations to Israel is that they are ignorant, essentially believing the word to mean “large numbers of civilian casualties.” (Here it’s worth noting that the United Nations, to little notice, has significantly lowered its estimate of the number of women and children killed in Gaza.) For others, accusing Israel of genocide is an emotional outlet for expressing outrage at such a horrific loss of life. A third, more pessimistic, characterization of the ubiquitous genocide canard is that it is only the latest iteration of the ancient antisemitic blood libel, which held that Jews murdered gentile children in order to use their blood for religious rituals.

College students and professional activists using overheated and imprecise language to convey their strongly held beliefs is hardly uncommon, and much of the intemperate language being directed at Israel and its Zionist supporters can be attributed to the hyperbole that increasingly characterizes our political discourse. What should worry us more is when people who have dedicated their lives to the written word manipulate language for a political end, one that is stigmatizing Jews.

Nine days after the Oct. 7 attack, the popular website Literary Hub began publishing what has since become a near-daily torrent of agitprop invective against what it describes as the “rogue ethnostate” of Israel, which it routinely accuses of committing genocide. In March, after a mass resignation of its staff members , the literary magazine Guernica retracted a personal essay by a left-wing Israeli woman about her experience volunteering to drive Palestinian children to Israel for medical treatment. In her resignation letter, one of the magazine’s co-publishers denounced the piece as “a hand-wringing apologia for Zionism and the ongoing genocide in Palestine.”

Whereas antisemitism in the literary world used to lurk in the shadows, according to the Jewish Book Council’s chief executive, Naomi Firestone-Teeter, since Oct. 7, it has become increasingly overt. “The fact that people have felt so proud and open about it is a different beast entirely,” she said. One of the most disturbing developments in this regard has been the frequency and contempt with which the word “Zionist” is now spit from people’s mouths in the United States.

Until relatively recently, the use of “Zionist” as a slur was most commonly confined to Soviet and Arab propagandists, who spent decades trying to render the word the moral equivalent of “Nazi.” Today many progressives use the word in similar fashion, making no distinction between a Zionist who supports a two-state solution (which, presumably, most Jews in the overwhelmingly liberal literary world do) and one who believes in a “Greater Israel” encompassing the entirety of the West Bank and Gaza Strip. And while anyone can be a Zionist, I’ve found in my 20 years of reporting on antisemitism that many Jews essentially hear “Jew” when someone shouts “Zionist" at them.

The corruption of the words “genocide” and “Zionist” lies at the root of the controversy threatening to unravel PEN America, the storied writers’ organization. As with many a literary contretemps, it involves a cascade of open letters. In February a missive that gained almost 1,500 signatures was published demanding that PEN “wake up from its own silent, tepid, neither-here-nor-there, self-congratulatory middle of the road and take an actual stand against an actual genocide.” The dozens of statements PEN had issued by that time calling attention to the plight of writers in Gaza (who the letter, without citing evidence, claimed had been “targeted” by Israel for assassination) were insufficient. “We demand PEN America release an official statement” about the writers killed in Gaza the letter read, “and name their murderer: Israel, a Zionist colonial state funded by the U.S. government.”

On March 20, PEN acceded to the ultimatum that it endorse the call for a cease-fire. But that did not satiate its critics.

Last month, in advance of PEN’s annual literary awards ceremony, nearly half of the nominated writers withdrew from the competition. A subset of those writers then released another open letter , declaring, “Among writers of conscience, there is no disagreement. There is fact and fiction. The fact is that Israel is leading a genocide of the Palestinian people.” They accused PEN of “normalizing genocide,” denounced PEN for its “platforming of Zionists” and, most shamefully, called for the resignation of its Jewish chief executive, Suzanne Nossel, on account of her “longstanding commitments to Zionism.”

Along with eight other past presidents of PEN, Salman Rushdie signed a letter in defense of the organization , an intervention that earned him an “unclear” rating on the anti-Zionist blacklist. (He has braved far worse from Islamist zealots and their Western apologists.) PEN ultimately canceled both the awards ceremony and subsequent World Voices Festival.

Dissatisfaction with PEN’s purported lack of indignation over the deaths of Palestinian writers is a fig leaf. Where were the efforts by those now decrying PEN to protest the complete absence of freedom of expression that has characterized the Gaza Strip under 17 years of Hamas rule?

The real objectives behind the cynical weaponization of the word “genocide” and the authoritarian insistence that anyone who disagrees with it is an enabler of one are to shut down debate, defame dissenters and impose a rigid orthodoxy throughout the publishing world. It is a naked attempt to impose an ideological litmus test on anyone hoping to join the republic of letters — a litmus test that the vast majority of Jews would fail.

A campaign of intimidation, the sort of thing that happens to the dissident writers in closed societies whom PEN regularly champions, is afoot to pressure writers into toeing this new party line. PEN’s current president, Jenny Finney Boylan, recently said that she had heard from “many, many authors who do not agree with those withdrawing from PEN events and who do not wish to withdraw from our events themselves but are afraid of the consequences if they speak up.”

Compelling speech — which is ultimately what PEN’s critics are demanding of it — is the tactic of commissars, not writers in a free society. Censorship, thought policing and bullying are antithetical to the spirit of literature, which is best understood as an intimate conversation between the author and individual readers.

PEN’s detractors aren’t helping the Palestinian people with their whitewashing of Hamas. They’re engaged in a hostile takeover of a noble organization committed to the defense of free expression in order to advance a sectarian and bigoted political agenda.

Neil Gaiman, Taylor Jenkins-Reid, Ms. Mandel and other hugely successful authors need not worry that being denounced as a Zionist will hurt their careers. But the blacklists and the boycotts do not really target them. The actual targets of this crusade are lesser-known authors, budding novelists, aspiring poets and creative writing students — largely but not exclusively Jewish — who can feel a change in the air.

“I do now definitely have concern as a Jewish author — two years working on a novel that has absolutely nothing to do with Jews in any way, just because it says ‘National Jewish Book Award winner’ in my bio — that it may change the way readers see the work,” said a Jewish creative writing professor and novelist who spoke to me on the condition of being quoted anonymously.

No longer is being on the receiving end of a review bomb the worst fate that can befall a Jewish writer exploring Jewish themes; even getting such a book published is becoming increasingly difficult. “It’s very clear you have to have real courage to acquire and publish proudly Jewish voices and books about being Jewish,” a prominent literary agent told me. “When you are seen as genocidal, a moral insult to humanity because you believe in Israel’s right to exist, you are now seen as deserving of being canceled.”

There’s a distasteful irony in a literary community that has gone to the barricades fighting book “bans” now rallying to boycott authors based on their ethnoreligious identity. For a growing set of writers, declaring one’s belief that the world’s only Jewish state is a genocidal entity whose dismantlement is necessary for the advancement of humankind is a political fashion statement, a bauble one parades around in order to signify being on the right team. As was Stalinism for an earlier generation of left-wing literary intellectuals, so is antisemitism becoming the avant-garde.

James Kirchick is a contributing writer to Tablet magazine, a writer at large for Air Mail and the author of “Secret City: The Hidden History of Gay Washington.”

The Times is committed to publishing a diversity of letters to the editor. We’d like to hear what you think about this or any of our articles. Here are some tips . And here’s our email: [email protected] .

Follow the New York Times Opinion section on Facebook , Instagram , TikTok , WhatsApp , X and Threads .

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• My Account Login
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Open access
• Published: 28 May 2024

Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction

• Alex E. Mohr   ORCID: orcid.org/0000-0001-5401-3702 1 , 2 ,
• Karen L. Sweazea 1 , 2 , 3 ,
• Devin A. Bowes   ORCID: orcid.org/0000-0001-9819-2503 2 ,
• Paniz Jasbi 4 , 5 ,
• Corrie M. Whisner   ORCID: orcid.org/0000-0003-3888-6348 1 , 2 ,
• Dorothy D. Sears   ORCID: orcid.org/0000-0002-9260-3540 1 ,
• Rosa Krajmalnik-Brown   ORCID: orcid.org/0000-0001-6064-3524 2 ,
• Yan Jin 6 ,
• Haiwei Gu 1 , 6 ,
• Judith Klein-Seetharaman   ORCID: orcid.org/0000-0002-4892-6828 1 , 4 ,
• Karen M. Arciero 7 ,
• Eric Gumpricht 8 &
• Paul J. Arciero   ORCID: orcid.org/0000-0001-7445-6164 7 , 9  

Nature Communications volume  15 , Article number:  4155 ( 2024 ) Cite this article

5347 Accesses

321 Altmetric

Metrics details

• Metabolomics
• Risk factors

The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P ( n  = 21) versus a heart-healthy, calorie-restricted (CR, n  = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p < 0.05), whereas metabolites associated with a longevity-related metabolic pathway increase with CR (p < 0.05). Differences indicate GM and metabolomic factors play a role in WL maintenance and body composition. This novel work provides insight into the GM and metabolomic profile of participants following an IF-P or CR diet and highlights important differences in microbial assembly associated with WL and body composition responsiveness. These data may inform future GM-focused precision nutrition recommendations using larger sample sizes of longer duration. Trial registration, March 6, 2020 (ClinicalTrials.gov as NCT04327141), based on a previous randomized intervention trial.

Similar content being viewed by others

Protein supplementation during an energy-restricted diet induces visceral fat loss and gut microbiota amino acid metabolism activation: a randomized trial

Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention

Intermittent fasting modulates the intestinal microbiota and improves obesity and host energy metabolism

Introduction.

As a principal modulator of the gut microbiome (GM) and weight status, nutritional input holds great therapeutic promise for addressing a wide range of metabolic dysregulation 1 . Dependent on the host for nutrients and fluid, one of the main processes by which the GM affects host physiology is producing bioactive metabolites from the gastrointestinal (GI) contents. Nutrient composition, feeding frequency, and meal timing impact this dependency 2 , 3 . To maintain a stable community and ecosystem, the GM must regulate its growth rate and diversity in response to nutrient availability and population density 4 . Such maintenance is affected by caloric restriction (CR) coupled with periods of feeding and intermittent fasting (IF) 5 . Moreover, we’ve recently shown the nutritional composition and meal frequency during these periods alter the metabolizable energy for the host 6 . The current study incorporates protein pacing (P), defined as four meals/day consumed evenly spaced every 4 h, consisting of 25–50 g of protein/meal 7 , 8 , 9 . Indeed, we have previously characterized a dietary approach of calorie-restricted IF-P combined and P alone 7 , 8 . These studies included nutrient-dense meal replacement shakes, along with whole foods, to quantitatively examine beneficial changes in body composition and cardiometabolic, inflammatory, and toxin-related outcomes in healthy and overweight individuals 7 , 8 , 10 , 11 , 12 . Further, recent preclinical work in mice has identified dietary protein as having anti-obesity effects after CR that are partially modulated through the GM 13 . Thus, the need to examine this in humans is warranted.

In this current work, we compare the effects of two low-calorie dietary interventions matched for weekly energy intake and expenditure; continuous caloric restriction on a heart-healthy diet (CR) aligned with current United States (US) dietary recommendations 14 versus our calorie-restricted IF-P diet 8 , 15 , in forty-one individuals with overweight or obesity, over an 8-week intervention. We hypothesize an IF-P diet may favorably influence the GM and metabolome to a greater extent than a calorie-matched CR alone. This exploratory investigation utilizes data and samples from a randomized controlled trial (NCT04327141) that compares the effects of the CR versus IF-P diet on anthropometric and cardiometabolic outcomes, as previously published 15 . As an additional analysis, we select “high” and “low” responders based on relative weight loss (WL) for a subgroup examination of the IF-P diet to better elucidate potential differential responses to intermittent fasting and protein pacing. Of special note, one individual lost 15% of their initial body weight over the 8-week intervention; this individual is followed longitudinally for a year to explore the dynamics of their GM and fecal metabolome. Novel findings from the current study shows an IF-P regimen results in improved gut symptomatology, a more pronounced community shift, and greater divergence of the gut microbiome, including microbial families and genera, such as Christensenellaceae , Rikenellaceae , and Marvinbryantia , associated with favorable metabolic profiles, compared to CR. Furthermore, IF-P significantly increases cytokines linked to lipolysis, weight loss, inflammation, and immune response. These findings shed light on the differential effects of IF-P as a promising dietary intervention for obesity management and microbiotic and metabolic health.

Intermittent fasting - protein pacing (IF-P) significantly influences gut microbiome (GM) dynamics compared to calorie restriction (CR)

We compared an IF-P vs. a CR per-protocol dietary intervention (matched for total energy intake and expenditure) over eight weeks to compare changes in weight, cardiometabolic outcomes, and the GM in men and women with overweight/obesity (IF-P: n  = 21; CR: n  = 20). One participant in each group were lost to follow-up due to non-compliance with dietary intervention (Fig.  1a ; CONSORT flow diagram: Supplementary Fig.  S1a ). The primary outcomes of dietary intake, body weight and composition responses, cardiometabolic outcomes, and hunger ratings after both dietary interventions are provided in our companion paper 15 . Briefly, after a one-week run-in period consuming their usual dietary intake (baseline diet), with no differences between groups at baseline for any dietary intake variable 15 , both dietary interventions significantly reduced total fat, carbohydrate, sodium, sugar, and energy intake by approximately 40% (~1000 kcals/day) from baseline levels (Fig.  1b ; Supplementary Data  1 ). By design, IF-P increased protein intake greater than CR during the intervention. The IF-P regimen consisted of 35% carbohydrate, 30% fat, and 35% protein for five to six days per week and a weekly extended modified fasting period (36–60 h) consisting of 350–550 kcals per day using randomization, as detailed previously 7 , 8 , 9 , 10 , 15 . In comparison, the CR regimen consisted of 41% carbohydrate, 38% fat, and 21% protein in accordance with current US dietary recommendations (Supplementary Table  S1 ) 14 , 16 . Using two-way factorial mixed model analysis of variance (ANOVA), significant macronutrient decreases drove energy reduction from dietary fat and carbohydrate ( p  < 0.001), with increased protein in the IF-P compared to CR ( p  < 0.001; Supplementary Fig.  S1b ; Supplementary Data  1 ). Regarding GI functioning and GM modulation, IF-P significantly decreased sugar and increased dietary fiber relative to CR (IF-P; pre, 20 ± 2 vs. post, 26 ± 2: CR; pre, 24 ± 3 vs. 24 ± 2 g/day; p  < 0.05). Despite similar average weekly energy intake (~9000 kcals/week) and physical activity energy expenditure (~350 kcals/day; p  = 0.260) during the intervention, participants following the IF-P regimen lost significantly more body weight (−8.81 ± 0.71% vs. −5.40 ± 0.67%; p  = 0.003; Fig.  1c ; Supplementary Data  1 ) and total, abdominal, and visceral fat mass and increased fat-free mass percentage (~2×; p  ≤ 0.030), as previously reported 15 . In addition, within-group analyses revealed a significant decrease in the reported frequency of total and lower-moderate GI symptoms (GI symptom rating score [GSRS] ≥4) over time for both IF-P and CR participants. However, when comparing the two dietary interventions at each time point, a more substantial reduction was observed in IF-P participants compared to CR participants (i.e., −9.3% vs. −5.4% and −13.2% vs. −3.9%, respectively; Table  1 ). The increased protein and lower sugar intake in IF-P compared to CR may have favorably mediated the GM and symptomatology.

a Study design with baseline participant characteristics. A registered dietitian counseled individuals from both groups each week. Time points with data collection are shown for both IF-P and CR participants. Icons created using BioRender.com. b Total daily caloric intake at each time point was not significantly different between IF-P and CR diet groups (two-sided Student’s t -test, p  < 0.05). Adjusted values are displayed by dividing total weekly intake by seven, to account for the fasting periods of IF-P. c IF-P participants lost significantly more weight over time versus CR participants. Points connected by line represent percent of weight compared to baseline weight for each participant. d Overall gut microbial colonization, as demonstrated by qPCR-based quantification of 16S rRNA gene copies per gram wet weight was unaffected by time or intervention (linear-mixed effects [LME] model, two-sided p  > 0.05). Alpha diversity metrics, e observed amplicon sequence variants (ASVs), and f Phylogenetic diversity at the ASV level significantly increased over time, independent of the intervention. g Intra-individual changes in GM community structure from baseline to weeks four and eight in IF-P participants shifted significantly throughout the IF-P intervention compared to CR as measured by the Bray-Curtis dissimilarity index (two-sided Wilcoxon rank-sum test). All box and whiskers plots display the box ranging from the first to the third quartile, and the center the median value, while the whiskers extend from each quartile to the minimum or maximum values. Heatmap of significant changes in h family- and i genus-level bacter i a by intervention. Colors indicate the within-group change beta coefficients over time for each cell, and asterisks denote significance. Black-white annotations on the bottom denote the significance of between-group change difference (by MaAsLin2 group × time interactions; p -values were corrected to produce adjusted values [ p .adj] using the Benjamini–Hochberg method). For all panels, IF-P: n  = 20, CR: n  = 19. Source data are provided as a Source Data file.

The substantial reduction in calorie intake of both groups (~40% from baseline) led us to investigate its potential impact on transient microbial colonization in the gut, as estimated by 16S rRNA gene copies (linear-mixed effects model [LME] time effect, p  = 0.114; Fig.  1d ; Supplementary Data  2 ). While it might be expected that a significant reduction in calorie intake could influence gut microbial colonization, our findings indicate that this reduction did not reach statistical significance within the timeframe of our study. This result contrasts with previous research that imposed more substantial energy restriction, such as a four-week regimen of ~800 kcal/day in participants with overweight/obesity, where overall gut microbial colonization notably decreased 4 . In addition to assessing microbial colonization, we also investigated whether the calorie reduction significantly influenced principal stool characteristics, including wet stool weight, Bristol stool scale (BSS), and fecal pH ( p  ≥ 0.066; Table  1 ). However, we did not observe statistically significant changes in these parameters over the course of the study. Moreover, there were no significant differences between the two dietary intervention groups over time (interaction effect, p  ≥ 0.051). In contrast, there were significant time effects for observed amplicon sequence variants (ASVs) and phylogenetic diversity (LME time effect, p  ≤ 0.023; Fig.  1e, f ; Supplementary Data  2 ), with values increasing at weeks four and eight compared to baseline (pairwise comparisons, p  ≤ 0.048); however, no interaction was observed for either alpha diversity metric (group × time effect, p  ≥ 0.925). To rule out the potential confounding effects of GI transit time 17 , BSS (as a surrogate marker) and stool pH were not significantly correlated with alpha diversity (Spearman correlations, p  ≥ 0.210). In relation to community composition, much of the intervention variance could be attributed to individual response upon testing nested permutational analysis of variance (PERMANOVA; R 2  = 0.749, p  = 0.001; Supplementary Table  S2 ), showcasing the highly individualistic landscape of the human GM in response to dietary intervention. However, a significant 1.8% of the variance was accounted for by the group × time interaction ( p  = 0.001). Moreover, individual responses over time showed variance between the two dietary interventions (PERMANOVA, R 2  = 0.123, p  = 0.003). This variability was apparent by assessing intra-individual differences, where a pronounced increase in Bray-Curtis dissimilarity was observed in the IF-P compared to the CR group after four (median Bray-Curtis dissimilarity, 0.53 [IQR: 0.47–0.61] vs. 0.38 [IQR: 0.33–0.47]) and eight weeks (0.50 [IQR: 0.41–0.55] vs. 0.39 [IQR: 0.33–0.45]; Fig.  1g ; Wilcoxon rank-sum test, p  ≤ 0.005).

To understand the taxa driving this GM variation from baseline to weeks four and eight between the two dietary interventions, we constructed MaAsLin2 linear-mixed models with the individual participant as a random factor 18 . We observed differential abundance patterns at the family and genus level in response to the IF-P but not the CR intervention. Of the 28 family and 69 genus-level features captured after filtering, a respective total of six and 18 taxa displayed significant interaction effects, with all significant time effects occurring from IF-P ( p .adj ≤ 0.10; Fig. 1h, i ; Supplementary Data  3 , 4 ). Notably, the changes observed at the four-week mark were more pronounced compared to those at eight weeks. These early alterations may signify an initial adaptation phase during which microbial populations respond to the modified substrate availability and nutrient composition, suggesting a degree of community resilience 19 . Increases were sustained to the third fecal collection for the family Christensenellaceae and the genera Incertae Sedis ( Ruminococcaceae family), Christensenellaceae R-7 group , and UBA1819 ( Ruminococcaceae family) (effect size > 2.0). Christensenellaceae is well regarded as a marker of a lean (anti-obesity) phenotype 20 and is associated with higher protein intake 21 . Other notable increases included Rikenellaceae , which, like Christensenellaceae , has been linked to reduced visceral adipose tissue and healthy metabolic profiles 22 , and Marvinbryantia , a candidate marker for predicting long-term weight loss success in individuals with obesity 23 . In addition, IF-P increased Ruminococcaceae , which has been noted to have an increased proteolytic and lipolytic capacity 24 . This shift in IF-P participants likely represents a change in GM substrate fermentation preferences as the diet regimen (relative protein and carbohydrate) and energy restriction is expected to increase the proteolytic: saccharolytic potential ratio 25 . In contrast, all taxa that decreased in IF-P participants were butyrate producers. These included the family Butyricicoccaceae and several genera such as Butyricicoccus (week four), Eubacterium ventriosum group (weeks four and eight), and Agathobacter (week four) (effect size < −2.0). When comparing monozygotic twin pairs, Eubacterium ventriosum group and another reduced genus, Roseburia , were more abundant in the higher body mass index (BMI) siblings 26 . Others, such as the mucosa-associated Butyricicoccus and Erysipelotricaceae UCG-003, have been positively correlated with insulin resistance and speculated to contribute to impaired glycolipid metabolism 27 .

Despite these changes in GM composition and increased fiber intake (+30% vs. baseline) of the IF-P participants 15 , we did not detect a significant shift in the abundance of the principal fecal short-chain fatty acids (SCFAs), acetate, propionate, butyrate, or valerate, as assessed by gas chromatography-mass spectrometry (GC–MS) (LME, p  ≥ 0.470; Supplementary Fig.  S1c ; Supplementary Data  5 ). Several factors likely contribute to this finding. For example, the distinct physical-chemical properties of fiber sources between IF-P and CR are inherently different. Participants adhering to the IF-P diet consumed most of their dietary fiber as liquid meal replacements (shakes) that are rich in non-digestible, oligosaccharide dietary-resistant starch 5 (RS5). In contrast, subjects on the CR regimen consumed their fiber from whole food sources such as vegetables, whole grains, and legumes. These fiber sources provided a mixture of soluble and insoluble fibers and a more complex fiber profile than IF-P participants. Moreover, even similar fiber profiles may function differently due to differences in food matrices and/or food preparation (cooking, raw consumption, etc.). Also of relevance is the timing of their fiber consumption. IF-P participants’ fiber intake was concentrated in fiber-rich shakes, offering immediate availability of fiber to the GI tract. In contrast, CR participants consumed fiber through whole foods, leading to a slower digestion and absorption process influenced by individual digestive transit times and enzymatic profiles. Interestingly, our results parallel recent work where participants more than doubled their fiber intake without affecting fecal SCFAs 28 . The disparate findings may be due to the type of dietary-resistant starch (RS) as a component of the nutrition regimen. In the current study, RS5 was included in the meal replacement shakes (eight grams/shake, two shakes/day, 16 g/day total). Prior research supports resistant starch intakes of >20 g/day favorably modulate SCFA production, primarily butyrate, over four to 12-week interventions 29 , 30 . Moreover, this lack of response in fecal SCFAs in both groups may have been further compounded by the significant reduction in energy intake in both groups, where the epithelia of the GI tract may have absorbed any potential increase in SCFAs from the dietary shift. It is worth noting that stool analysis may not be the most reliable biological surrogate for capturing SCFA flux over time 28 . Nevertheless, the changes in nutrient quality, timing, ratios, and the observed shift toward proteolytic activity suggest that the luminal matrix of digesta in the IF-P group impacted substrate availability for GM. This effect appears to be an influencing force in driving the observed beneficial shifts in microbial communities, such as Christensenellaceae and Incertae Sedis , as well as improvements in GI symptomatology in IF-P compared to CR. These results underscore the complexity of dietary influences on GM and highlight the need for further research to explore the impact of liquid meal replacements versus whole food sources on GM changes and SCFA status.

IF-P modulates circulating cytokines and gut microbiome taxa compared to CR

Caloric restriction and WL have been well known to positively influence inflammatory cytokine expression, with GM now emerging as an important modulator 31 . Surveying a panel of 14 plasma cytokines, we noted significant interaction (group × time) effects for IL-4, IL-6, IL-8, and IL-13 (LME, p  ≤ 0.034; Fig.  2a–d ; Supplementary Table  S3 ; Supplementary Data  6 ). These cytokines exhibited increases at weeks four and/or eight compared to baseline exclusively in the IF-P group (pairwise comparisons, p .adj ≤ 0.098), while no significant changes were observed in the CR group ( p .adj ≥ 0.562). Notably, IL-4 has been reported to display lipolytic effects 32 , and IL-8 has been positively associated with weight loss and maintenance 33 . Regarded as a proinflammatory myokine, IL-6 can acutely increase lipid mobilization in adipose tissue under fasting or exercise conditions 34 , 35 , 36 . IL-13 may be important for gut mucosal immune responses and is a stimulator of mucus production from goblet cells 37 , which has been recently reported to be influenced during a two-day-a-week fasting regimen in mice 38 . These results were of note considering the significant total body weight, fat, and visceral fat loss in the IF-P compared to the CR group. Surprisingly, correlational analysis with change (post – pre) in anthropometric and select plasma biomarker values with the cytokine profile did not reveal any significant associations after correcting for multiple testing effects ( p .adj ≥ 0.476; Supplementary Data  7 ). Plasma cytokines were, however, correlated with microbial composition for samples collected in the IF-P group during the intervention period (weeks four and eight) using graph-guided fused least absolute shrinkage and selection operator (GFLASSO) regression, revealing associations between cytokine-taxa pairs (Supplementary Fig.  S2a ). Of the four cytokines that increased in IF-P participants, we identified multiple significant correlations: Colidextribacter (rho = −0.55, p .adj = 0.015), Ruminococcus gauvreauii group (rho = 0.50, p .adj = 0.036), and Intestinibacter (rho = 0.45, p .adj = 0.086) with IL-4 (Supplementary Fig.  S2b ) and an unclassified genus from Oscillospiraceae (rho = −0.53, p .adj = 0.019), Colidextribacter (rho = −0.52, p .adj = 0.019), and Ruminoccus gauvreauii group (rho = 0.51, p .adj = 0.019) with IL-13 (Supplementary Fig.  S2c ).

a IL-4, b IL-6, c IL-8, and d IL-13: Each panel shows the cytokine concentration levels. Significant time effects and interaction effects (group × time) were detected using linear-mixed effects models (LME, two-sided p  < 0.05), indicating differential changes over the intervention period. IF-P participants exhibited significant increases in cytokine levels compared to baseline, as evidenced by pairwise comparisons adjusted for multiple testing using the Benjamini–Hochberg method (two-sided p .adj < 0.10). All box and whiskers plots display the box ranging from the first to the third quartile, and the center the median value, while the whiskers extend from each quartile to the minimum or maximum values. For all panels, IF-P: n  = 20, CR: n  = 19. Source data are provided as a Source Data file.

Displaying negative correlations for IL-4 and IL-13, Colidextribacter has been shown to be positively correlated to fat accumulation, insulin, and triglyceride levels in mice fed a high-fat diet 39 and positively correlated with products of lipid peroxidation, suggesting its potential role in promoting oxidative stress 40 . Conversely, Ruminoccus gauvreauii group was positively correlated with IL-4 and IL-13. Although limited information is available regarding the host interactions of this microbe, this genus is considered a commensal part of the core human GM and able to convert complex polysaccharides into a variety of nutrients for their hosts 41 . While these findings highlight the potential interplay between specific microbes and cytokine profiles, the directional influence—whether microbial changes drive cytokine alterations or vice versa—cannot be determined in this study setting. Furthermore, despite the change in cytokine profiles in the IF-P group, we did not detect any significant time or group × time effects when measuring lipopolysaccharide-binding protein (LBP; Δ pre/post, IF-P: 0.24 ± 0.31 vs CR: −0.93 ± 0.49 μg/mL; p  ≥ 0.254), a surrogate marker for gut permeability 42 . While the GM plays a crucial role in modulating the gut-immune axis, the observed cytokine fluctuations and microbial associations might also involve other factors. These include the production of specific metabolites due to shifts in microbial composition as well as the influence of the dietary regimen itself, which may have a central role in shaping these interactions.

IF-P and CR yield distinct circulating metabolite signatures and convergence of multiple metabolic pathways

To understand the potential differential impact of IF-P versus CR on the host, we surveyed the plasma metabolome, reliably detecting 136 plasma metabolites across 117 samples (i.e., QC CV < 20% and relative abundance > 1000 in 80% of samples). Based on outlier examination (random forest [RF] and principal component analysis [PCA]), no samples were categorized as outliers, and all data were retained for subsequent analysis. Metabolomic profile shifts were observed in both IF-P and CR groups compared with baseline (Canberra distance), however, these did not differ significantly by group or time (weeks four and eight; Wilcoxon rank-sum test, p  ≥ 0.087; Supplementary Fig.  S3a ). We prepared a general linear model (GLM) with age, sex, and time as covariates and corrected for false discovery rate (FDR). When controlling for these relevant covariates, we observed significant differences between IF-P and CR for 15 metabolites (Fig.  3a , Supplementary Table  S4 ): 2,3-dihydroxybenzoic acid, malonic acid, choline, agmatine, protocatechuic acid, myoinositol, oxaloacetic acid, xylitol, dulcitol, asparagine, n-acetylglutamine, sorbitol, cytidine, acetylcarnitine, and urate ( p .adj ≤ 0.089). To estimate the univariate classification performance of the 15 significant metabolites, we performed a receiver operating characteristic (ROC) analysis. Ten metabolites demonstrated a moderate area under the curve (AUC) (0.718–0.819), while five metabolites had an AUC < 0.70. Therefore, to improve classification performance, we constructed a supervised PLS-DA model using levels of the 15 significant metabolites ( p .adj ≤ 0.089) and analyzed variable importance in projection (VIP) scores (Supplementary Fig.  S3b ). Five metabolites with a VIP > 1.0 (2,3-dihydroxybenzoic acid, malonic acid, protocatechuic acid, agmatine, and myoinositol) were retained to construct an enhanced orthogonal projection to latent structures discriminant analysis (OPLS-DA) model. In contrast, the model fit was assessed with 100-fold leave-one-out cross-validation (LOOCV; see “Methods” section). Permutation testing showed the refined OPLS-DA model to have an acceptable fit to data ( Q 2  = 0.460, p  < 0.001), with appreciable explanatory capacity ( R 2  = 0.506, p  < 0.001; Supplementary Fig.  S3c ). The ROC analysis produced an area under the curve (AUC) of 0.929 (95% CI: 0.868–0.973, sensitivity = 0.8, specificity = 0.9; Supplementary Fig.  S3d ) between the CR and IF-P groups showing good accuracy of the GLM and providing strong support for the differential expression of these 15 metabolites between groups.

a Abundance and log fold-change of significant plasma metabolites between IF-P and CR groups as determined by a general linear model (GLM) adjusted for age, sex, and time. All GLM analyses utilized two-sided p -values, with multiple testing corrections applied using the Benjamini–Hochberg method ( p .adj). Metabolome pathway analysis was conducted for b IF-P and c CR using all reliably detected metabolites showing significantly altered pathways ( p .adj < 0.10) with moderate and above impact (>0.10). Impact scores were calculated using a hypergeometric test, while significance was assessed via a test of relative betweenness centrality, emphasizing the changes in metabolic network connectivity. For all panels, IF-P: n  = 20, CR: n  = 19. Source data are provided as a Source Data file.

Two metabolites, malonic acid, and acetylcarnitine, increased compared to the CR intervention. Several other investigators have noted the increase in acetylcarnitine via fasting protocols 43 , 44 . This increase is consistent with free fatty acid mobilization and increased transportation of these fatty acids via carnitine acylation into the mitochondria for fatty acid oxidation. These results would also be consistent with the expected ketogenesis, although not documented in our study, but noted by similar fasting interventions 44 . Relatedly, malonic acid, a naturally occurring organic acid, is a key regulatory molecule in fatty acid synthesis via its conversion to acetoacetate; hence, our results may reflect this increased synthesis in response to the mobilization and oxidation of fatty acids occurring during fasting. Other metabolites that decreased with IF-P include several sugar alcohols (myoinositol, dulcitol, and xylitol). Dulcitol (galactitol) is a sugar alcohol derived from galactose. It is possible that during fasting, levels of dulcitol decrease as glucose (initially) and free fatty acids (after 24–36 h of fasting) are preferentially utilized as energy substrates. One amino acid (asparagine) and one amino acid analog (N-acetylglutamine, associated with consumption of a Mediterranean diet 45 ) also decreased with IF-P relative to CR. Finally, 2,3-dihydroxybenzoic acid significantly decreased with IF-P. This metabolite is formed during the metabolism of flavonoids, as it is found abundantly in fruits, vegetables, and some spices. At the cellular level, this hydroxybenzoic acid functions as a cell signaling agent and has been speculated as a potentially protective molecule in various cancers 46 . It is unclear whether this metabolite decreased due to either dietary intake or metabolic processes related to high-protein intake or the fasting protocol. Collectively, the metabolic responses to these dietary regimens reflect the interrelationships of several anabolic and catabolic physiologic responses to three key components of these interventions: (a) the WL process itself, (b) changes in amount (and type) of macronutrient distribution (i.e., meal replacement shakes vs. whole food diet approach; higher vs. normal protein intakes), and (c) the adherence to fasting (IF-P only).

To determine the significantly impacted pathways of the dietary interventions, we grouped participant samples according to baseline or intervention period (weeks four and eight), with IF-P and CR assessed separately. A total of 14 pathways were significant in the IF-P group ( p .adj < 0.10; Fig.  3b ), with three displaying large impact coefficients (>0.5): (1) Glycine, serine, and threonine metabolism, (2) alanine, aspartate, and glutamate metabolism, and (3) ascorbate and aldarate metabolism. In comparison, 24 pathways were significant for the CR group (Fig.  3c ), with four showing large impact coefficients (>0.5): (1) Phenylalanine, tyrosine, and tryptophan biosynthesis, (2) alanine, aspartate, and glutamate metabolism, (3) citrate cycle (TCA cycle), and (4) glycine, serine and threonine metabolism. Notably, the glycine, serine, and threonine pathway has recently been found in preclinical models to play a pivotal role in longevity and related life-sustaining mechanisms independent of diet, though heavily impacted by fasting time and caloric restriction 47 . This may be partially related to the ability of glycine to increase tissue glutathione 48 , 49 and protect against oxidative stress 50 . In our analysis, this pathway was significant in both diet groups and is biochemically and topologically related to the additionally captured amino acid pathway, alanine, aspartate, and glutamate metabolism, as well as the energy-releasing pathway, the citrate cycle (TCA cycle). Notably, in the CR group, phenylalanine, tyrosine, and tryptophan biosynthesis, are important for neurotransmitter production and reported to be suppressed (tryptophan) in obesity 51 . This representation may have also been attributed to the differences in protein intake 52 or differences in dietary diversity 53 , yet to be determined. Regardless, we noted similar representations of pathway impact between IF-P and CR, with metabolic response centered on utilization of amino acids in addition to lipid turnover and energy pathways.

Gut microbiome and plasma metabolome latent factors indicate differential multi-omic signatures between IF-P and CR regimens

As the plasma metabolome has been suggested as a bidirectional mediator of GM influence on the host 54 , we performed a multi-omics factor analysis (MOFA) 55 to identify potential patterns of covariation and co-occurrence between the microbiome and circulating metabolites. Operating in a probabilistic Bayesian framework, MOFA simultaneously performs unsupervised matrix factorization to obtain overall sources of variability via a limited number of inferred factors and identifies shared versus exclusive variation across multiple omic data sets 55 . Eight latent factors were identified (minimum explained variance ≥2%; see “Methods” section), with the plasma metabolome and GM explaining 37.12% and 17.49% of the overall sample variability, respectively (Fig.  4a ). Based on significance and the proportion of total variance explained by individual factors for each omic assay, Factors 1 ( R 2  = 11.98) and 6 ( R 2  = 5.28) captured the greatest covariation between the two omic layers (Fig.  4a ; Supplementary Table  S5 ). In contrast, Factors 2 and 5 were nearly exclusive to the metabolome, and factors 3 and 4 to the GM. Interestingly, Factor 1 was significantly negatively correlated to dietary protein intake (Spearman rho = −0.270, p.adj = 0.021; Fig.  4b ) and captured the variation associated with the CR diet (Wilcoxon rank-sum test, p .adj = 3.2e-04; Fig.  4c ). Factor 6 had the greatest number of significant correlations, including negative associations with visceral adipose tissue, waist circumference, body weight, BMI, fat mass, android fat, subcutaneous adipose tissue, dietary sodium, carbohydrate, fat, energy intake (kcal), and sugar (Spearman rho ≤ −0.220, p .adj ≤ 0.075) and captured the variation associated with IF-P (Wilcoxon rank-sum test, p .adj = 0.007).

a The cumulative proportion of total variance explained ( R 2 ) and proportion of total variance explained by eight individual latent factors for each omic layer. b Spearman correlation matrix of the eight latent factors and clinical anthropometric and dietary covariates. Each circle represents a separate association, with the size indicating the significance (-log10 ( p -values)) and the color representing the effect size (hue) with its direction (red: positive; blue: negative). All correlations are calculated using two-sided tests. Asterisks within a circle denote significance after adjustment with the Benjamini–Hochberg method. c Scatter plot of Factors 1 and 6, with each dot representing a sample colored by intervention. Box and whisker plots illustrate significant differences between groups after adjusting for multiple testing using the Benjamini–Hochberg method (Wilcoxon rank-sum test; top = Factor 1, p .adj = 3.2e-04; right = Factor 6, p .adj = 0.007). The plots show boxes ranging from the first to the third quartile and the median at the center, with whiskers extending to the minimum and maximum values. d Factor 1 and 6 loadings of genera and metabolites with the largest weights annotated. Symbols: * p .adj < 0.10, ** p .adj < 0.01, *** p .adj < 0.001, **** p .adj < 1.0e-04. For all panels, IF-P: n  = 20, CR: n  = 19. Source data are provided as a Source Data file.

Assessing the positive weights (feature importance) of Factor 1 revealed a microbial and metabolomic signature linked with CR, including the taxa Faecalibacterium , Romboutsia , and Roseburia , and the plasma metabolites myoinositol, agmatine, N-acetylglutamine, erythrose, and mucic acid (Fig.  4d ). Previous dietary restriction studies have reported co-occurrence of gut microbial taxa and plasma metabolites that span a wide variety of applications and investigations 56 . The specific co-occurrences observed in Factor 1 exhibited an abundance of butyrate-producing bacterial taxa that utilize carbohydrates as their predominant substrate and plasma metabolites that are generally involved in carbohydrate metabolism, such as erythrose, an intermediate in the pentose phosphate pathway (PPP), and mucic acid which is derived from galactose and/or galactose-containing compounds (i.e., lactose). These co-occurrence patterns biologically cohere considering the nutritional profile of the CR group and the large contribution of fiber-rich, unrefined carbohydrates and reduction in sugar (~50% kcal from sugar). Indeed, these nutritional changes may have influenced the GM to accommodate changes in dietary substrate more efficiently. One interesting co-occurrence was the genus Romboutsia and metabolite N-acetylglutamine. Romboutsia has been shown to produce several SCFAs and ferment certain amino acids, including glutamate 57 . N-acetylglutamine is biosynthesized from glutamate; thus, its co-occurrence with the abundance of Romboutsia encourages further exploration into this interaction 58 .

Factor 6 captured the signature associated with IF-P, with positive contributions from the taxa Incertae Sedis ( Ruminococcaceae family), Erysipelatoclostridium , Christensenellaceae R-7 group , Oscillospiraceae UCG-002, and Alistipes , and the plasma metabolites malonic acid, adipic acid, succinate, methylmalonic acid, and mucic acid (Fig.  4d ). Prior work has established that Alistipes increases from diets rich in protein and fat, and contributes to the highest number of putrefaction pathways (i.e., fermentation of undigested proteins in the GI tract) over the other commensals 59 . This could explain the co-occurrence of plasma metabolites from protein catabolism, such as 2-aminoadipid acid, adipic acid, and glutamic acid 22 , 59 . Oscillospiraceae has recently been viewed with next-generation probiotic potential, harboring positive regulatory effects in areas related to obesity and chronic inflammation 60 . Mentioned prior, recent studies have reported on the role of Christensenellaceae on human health, participating in host amino acid and lipid metabolism as well as fiber fermentation 20 , with Christensenellaceae R-7 group notably evidenced to correlate with visceral adipose tissue reduction 22 . As such, the elevated abundance of microbes in the GM of IF-P participants observed in this study in tandem with the co-occurrence of metabolites indicative of protein degradation and mobilization and oxidation of fatty acids, such as methylmalonic acid, malonic acid, and succinate, presents a nascent multi-omic signature of IF-P. In addition, and more pronounced in the IF-P vs CR group, participants decreased sugar intake by ~75% (kcals) compared to baseline levels. Considering the other regimental components of IF-P, the differences in multi-omic signatures likely display the selective pressures of these two interventions.

Gut microbiome (GM) composition is associated with weight loss (WL) responsiveness to IF-P diet

The IF-P intervention produced a microbiome and metabolomic response; however, the loss in body weight and fat across individuals varied (Fig.  5a ). To provide deeper characterization and explore differential features of WL responsiveness, we performed a GM-focused subgroup analysis by employing shotgun metagenomic and untargeted fecal metabolomic surveys in 10 individuals that either achieved ≥10% loss in body weight or bordered on clinically important WL (i.e., >5% BW; herein, ‘High’ and ‘Low’ responders) 61 . Importantly, baseline characteristics between WL responder classification did not differ significantly (baseline body weight: High, 108.9 ± 30.8 vs. Low, 81.9 ± 18.1 kg, p  = 0.117; Supplementary Table  S6 ). Assessing the GM at the fundamental taxonomic rank, species composition showed significant separation by weight loss response evaluated by Bray-Curtis dissimilarity (group × time: R 2  = 0.114, p  = 0.001; Fig.  5b ; Supplementary Table  S7 ), with most of the variation explained by the individual ( R 2  = 0.711, p  = 0.001). In comparison, species level alpha diversity did not differ significantly between classifications (group × time: p  ≥ 0.674; Fig.  5c, d ). Identifying 212 species after filtering, we noted significant differences in bacterial abundances between groups over time (Fig.  5e ; Supplementary Data  8 ). A total of 10 features increased in the High-responder group relative to the Low-response group over the eight-week study period, including Collinsella SGB14861 , Clostridium leptum , Blautia hydrogenotrophica , and less typified species; GGB74510 SGB47635 (unclassified Firmicutes), GGB3511 SGB4688 (unclassified Firmicutes), Faecalicatena contorta , Lachnospiraceae bacterium NSJ-29 , Phascolarctobacterium SGB4573 , GGB38744 SGB14842 (unclassified Oscillospiraceae ), and Massiliimalia timonensis (effect size ≥ 1.163, p .adj ≤ 0.092). The increase in Collinsella , a less characterized anaerobic pathobiont that produces lactate and has been associated with low-fiber intakes 62 , 63 and lipid metabolism 64 , may have been related to the periods of CR and IF, in conjunction with the greater influx of host-released fatty acids in the High-responder group. Relatedly, Clostridium leptum growth has been linked with increases in monounsaturated fat intake, reductions in blood cholesterol 65 , and stimulation of Treg induction (i.e., anti-inflammatory) 66 . The latter association is relevant to the SCFA-promoting (primarily butyrate) qualities of Clostridium leptum 67 . Blautia hydrogenotrophica , an acetogen with bidirectional metabolic cross-feeding properties (e.g., transfer of hydrogen and acetate), is also important for butyrate formation 68 . Taxa that decreased relative to the Low-responder group; Eubacterium ventriosum , Streptococcus salivarius , Eubacterium rectale , Anaerostipes hadrus , Roseburia inulinivorans , Mediterraneibacter glycyrrhizinilyticus , and Blautia massiliensis (effect size ≤ −1.690, p .adj ≤ 0.078), included butyrate producers, Eubacterium ventriosum , Eubacterium rectale , Roseburia inulinivorans , and others, such as Streptococcus salivarius , a nuclear factor kappa B (NF-κB) activity repressor 69 and Peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor potentially influencing lipid and glucose metabolism 70 . Investigating monozygotic (MZ) twin pairs, Eubacterium ventriosum was more abundant in the higher BMI siblings 26 , with enhanced scavenging fermentation capabilities 71 . Roseburia inulinivorans is a mobile firmicute (flagella) that harbors a wide-ranging enzymatic repertoire able to act on various dietary polysaccharide substrates suggestive of the ability to respond to the availability of alternative dietary substrates 72 . While we noted a more variable shift in fecal total SCFAs, acetate, propionate, butyrate, or valerate (via targeted GC–MS), in the Low weight loss responders, there was no significant difference when compared to High weight loss responders (Wilcoxon rank-sum test, p  ≥ 0.210; Supplementaryl Fig.  S4a ; Supplementary Data  9 ).

a Relative weight loss over the eight-week intervention for each participant in the IF-P group. b NMDS ordination showed the personalized trajectories of participants’ microbiomes over time. Dotted lines connect the same individual and point toward the final sample collection. No significant time or group × time interaction effects for alpha diversity metrics, c observed species, and d the Shannon index. Box and whiskers plots display the box ranging from the first to the third quartile, and the center the median value, while the whiskers extend from each quartile to the minimum or maximum values. Volcano plots displaying differential abundance between High and Low weight loss responders for e microbial species and f functional pathways. Significant features were more enriched in High and Low weight loss responders colored orange and light blue, respectively. g Alluvial plot displaying the fecal metabolite profile at the subclass level (Human Microbiome Database). Most abundant metabolite subclasses displayed (i.e., ≥1%). Metabolome pathway analysis for h High and i Low weight loss responders using all reliably detected fecal metabolites showing altered pathways with moderate and above impact (>0.10). Impact was calculated using a hypergeometric test, while significance was determined using a test of relative betweenness centrality. j Grid-fused least absolute shrinkage and selection operator (GFLASSO) regression of species from differential abundance analysis displayed correlative relationships with fecal metabolites. Species with greater abundance in High (High > Low) and Low (Low > High) weight loss responders are separate‘. For all panels, High: n  = 5, Low: n  = 5. Source data are provided as a Source Data file.

Less affected compared to taxonomic features were the 275 microbial-affiliated metabolic pathways identified after filtering, of which gluconeogenesis III and guanosine ribonucleotides de novo biosynthesis were increased (effect size ≥ 0.108, p .adj = 0.079), while super pathway of L-alanine biosynthesis, sucrose degradation IV (sucrose phosphorylase), sucrose degradation III (sucrose invertase), super pathway of thiamine diphosphate biosynthesis III, and flavin biosynthesis I (bacteria and plants) were decreased in the High relative to the Low weight loss responder group (effect size ≤ −0.247, p .adj ≤ 0.079; Fig.  5f ; Supplementary Data  10 )

As the difference in microbial shifts versus function is well established, we also tracked the fecal metabolome to better understand metabolic modification/production and identify potential microbial metabolic targets for future weight loss interventions. Overall, we reliably detected (QC relative standard deviation > 20% and mean intensity value > 1000 in 80% of samples) and annotated 607 (Human Metabolome Database) compounds across fecal samples. Notably, we found the fecal metabolite profile of both subgroups abundant in amino acids, peptides, and analogs, with decreases in sulfates, furanones, and quaternary ammonium salts and increases in cholestane steroids, carboxylic acid derivatives, and imidazoles (Fig.  5g ). Assessing metabolite changes between groups did not yield significance when comparing logFC values (Wilcoxon rank-sum test, p .adj > 0.10; Supplementary Fig.  S4b ). Pathway analysis of High weight loss responders revealed prominent metabolic signatures relevant to lipid metabolism (glycerolipid and arachidonic metabolism), nucleotide turnover (pyrimidine metabolism), and aromatic amino acid formation (phenylalanine, tyrosine, and tryptophan biosynthesis; Fig.  5h , Supplementary Data  11 ). In comparison, the more prominent enriched pathways for Low weight loss responders included those related to amino acid and peptide metabolism (glycine, serine, and threonine, d-glutamine and d-glutamate, and tyrosine metabolism and arginine biosynthesis; Fig.  5i , Supplementary Data  12 ).

Finally, species captured by our differential abundance analysis were channeled into a GFLASSO model with the fecal metabolome library to select metabolically relevant compounds best predicted by microbial abundances. Restricting taxa and metabolites displaying stronger co-occurrence signals (GFLASSO coefficients > 0.02), we noted several patterns (Fig.  5j ). This included positive associations between GGB3511 SGB4688 (unclassified Firmicute) and malonic acid (important to fatty acid metabolism), as well as Roseburia inulinivorans and 3-Hydroxy-2-oxo-1H-indole-3-acetic acid. Negative associations included Phascolarctobacterium SGB4573 with the fatty acid ester, methyl sorbate, and Streptococcus salivarius (anti-inflammatory) with leukotriene B4 dimethylamide.

Differences detected in our subgroup analysis suggest that the GM composition plays a role in WL responsiveness during IF-P interventions. Notable differences in taxa and fecal metabolites suggest differing substrate utilization capabilities and nutrient-acquiring pathways between High and Low responders, despite being on the same dietary regimen. Although differences between High and Low responders were statistically significant for the microbiome data, the magnitude of differences varied, suggesting further research is needed to clarify these differences.

Long-term IF-P remodels the gut microbiome after substantial weight loss – A case study

Considering the microbiomic and metabolic importance of sustained WL, we additionally performed a longitudinal, exploratory case study analysis on the participant who lost the most body weight during the eight-week WL period (−15.3% BW, −24.9 kg). Under rigorous clinical supervision, this individual was guided through and comprehensively tracked over 52 weeks, strictly adhering to an IF-P regimen, including WL (0–16 weeks) and maintenance (16–52 weeks) periods, which included adjusting the calorie intake to maintain energy balance. Microbial richness and evenness at the species level displayed a general inverse trend with body weight reduction, although they converged at 52 weeks (Fig.  6a, b ). Species dissimilarity peaked at weeks four and 16, after which it plateaued, but remained consistently higher in comparison to baseline over the 52-week period (Fig.  6c ). Examining positive linear coefficients of a PERMANOVA model, constructed to detect variation between community compositions over time, dominant influences included several species within the Lachnospiraceae family such as Fusicatenibacter saccharivorans , Blautia wexlerae , Blautia massillensis , Anaerostipes hadrus , and Coprococcus comes and others like Akkermansia muciniphila (Fig.  6d ). Negative contributions included species from the Oscillospiraceae family, such as Ruminococcus bromii and Ruminococcus torques . Indeed, visualizing community composition over the sampling time points suggested specific GM remodeling (Fig.  6e ; Supplementary Data  13 ). Many keystone taxa prominent over time in the microbiome are highly relevant to the significant reduction in body weight and metabolic improvement of the case-study participant. For example, Blautia wexlerae , a commensal bacterium recently reported to confer anti-adipogenesis and anti-inflammatory properties to adipocytes 73 became visually more prominent over time. This association was also the case for the health-associated microbe, Anaerostipes hadrus , which converts inositol stereoisomers (including myoinositol) to propionate and acetate, apt to improve insulin sensitivity and reduce serum triglyceride levels 74 , translating to reduced host metabolic disease risk 75 . Other elevated taxa, like the mucin-degrading Akkermansia muciniphila and Bacteroides faecis , are negatively correlated with markers for insulin resistance 76 . There was also a notable bloom of Collinsella SGB14861 (anaerobic pathobiont producing lactate) 63 and suppression of Eubacterium rectale , Ruminococcus torques (associated with circadian rhythm disruption in mice) 77 , and Ruminococcus bromii (an exceptional starch degrader) 78 .

Change in alpha diversity metrics a observed species and b Shannon index with percentage of baseline body weight. c Bray-Curtis dissimilarity at the species level with d top PERMANOVA model coefficients (analysis: species~time). e Alluvial plot displaying the variation in abundance of the 20 most prevalent bacteria over time. For visual clarity, the less abundant taxa are not displayed. f Canberra distance of fecal metabolome with g top PERMANOVA model coefficients (analysis: pathway~time). h Pathway analysis of fecal metabolites comparing baseline to subsequent sample collections. Data are plotted as -log10(p) versus pathway impact. Node size corresponds to the proportion of metabolites captured in each pathway set, while node color signifies significance. Impact was calculated using a hypergeometric test, while significance was determined using a test of relative betweenness centrality. No p -value adjustments were made. Source data are provided as a Source Data file.

Compared to the more pronounced shifts in the GM, an inspection of Bray-Curtis dissimilarity at the microbial metabolic pathway level was much less affected (Supplementary Fig.  S5a ). Though positive contributions in multiple biosynthesis pathways were noted, as well as reductions in the superpathway of UDP-glucose-derived O-antigen building blocks biosynthesis and glucose and glucose-1-phosphate degradation (Supplementary Fig.  S5b ; Supplementary Data  14 ). We also tracked the fecal metabolome concordance with the GM to corroborate potential metabolic output. Shifts in metabolites captured by calculating the Canberra distance were prominent (Fig.  6f ), with positive influences from agrocybin (possessing antifungal activity 79 ), nicotinic acid (nicotinamide adenine dinucleotide precursor), and sulfate, and reductions in cadaverine (involved in the inhibition of intestinal motility 80 ), maltitol, acetohydroxamic acid (a urease inhibitor), and hypoxanthine, after removing the dominant amino acid subclass (Fig.  6g ; Supplementary Fig.  S5c ). At the chemical class level, we observed apparent shifts in chemical subclasses; cholestane steroids, amines, purines, and purine derivatives, and amino acids, peptides, and analogs (Supplementary Fig.  S5d ). Given our case-study approach, we performed a pathway analysis using all reliably detected fecal metabolites at each collection point over 52 weeks. Pathway analysis (Fig.  6h ) identified primary bile acid biosynthesis ( p  = 0.014) and cysteine and methionine metabolism ( p  = 0.096) as having the greatest significance, while the greatest impact (I) was observed in phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism ( I  = 1.0). Alanine, aspartate, and glutamate metabolism ( I  = 0.756), vitamin B6 metabolism ( I  = 0.647), sulfur metabolism ( I  = 0.532), phenylalanine metabolism (I =  0.357), and nicotinate and nicotinamide metabolism ( I  = 0.194) also displayed marked pathway impacts (Supplementary Fig.  S5e ; Supplementary Data  15 ). Together, these integrated findings from the group comparisons (IF-P vs. CR), high vs. low responders, and the case study, suggest that the remodeling of the gut microbiome through sustained weight loss on an IF-P regimen not only alters the microbial composition but also influences key metabolic pathways and output, reflective of fat mobilization and metabolic improvement.

Our study demonstrates distinct effects of IF-P on gut symptomatology and microbiome, as well as circulating metabolites compared to continuous CR. We observed significant changes in the GM response to both interventions; however, the IF-P group exhibited a more pronounced community shift and greater divergence from baseline (i.e., intra-individual Bray-Curtis dissimilarities). This shift was characterized by increased specific microbial families and genera, such as Christensenellaceae , Rikenellaceae , and Marvinbryantia , associated with favorable metabolic profiles. Furthermore, IF-P significantly increased circulating cytokine concentrations of IL-4, IL-6, IL-8, and IL-13. These cytokines have been linked to lipolysis, WL, inflammation, and immune response. The plasma metabolome analysis revealed distinct metabolite signatures in IF-P and CR groups, with the convergence of multiple metabolic pathways. These findings shed light on the differential effects of IF regimens, including IF-P as a promising dietary intervention for obesity management and microbiotic and metabolic health.

While acknowledging individual contributions of WL, protein pacing, and IF, we propose that the beneficial shifts observed may be best characterized as the culmination of features inherent in our IF-P approach. For example, it is possible that microbial competition is leveraged during reduced and intermittent nutritional input periods, emphasizing nutrient composition and food matrix type (combination of whole food and meal replacements vs. primarily whole food), affecting available substrates for gut microbes. IF-P participants’ fiber intake was concentrated in fiber-rich (RS5 type) shakes, offering immediate availability of fiber to the GI tract. In contrast, CR participants consumed fiber through whole foods, leading to a slower digestion and absorption process influenced by individual digestive transit times and enzymatic profiles. This nutritional environment may create ecological niches that support symbiont microbial communities. In this investigation, we provide support of such remodeling, with intentional fasting and increased relative protein (protein pacing) consumption well-validated to improve body composition and metabolism during weight loss 7 , 8 , 15 . Our results align with previous studies on CR, where greater relative protein intake was associated with an increased abundance of Christensenella 81 . This increase is likely a result of increased amino acid-derived metabolites 21 . We also observed increased signatures of amino acid metabolism in the GM of IF-P participants, which may be attributed to increased nitrogen availability, prompting de novo amino acid biosynthesis. The liquid format of two of the daily meals and precise timing of high-quality protein consumption (Protein Pacing) in the IF-P regimen may have influenced these results, as amino acids play essential roles in microbial communities, acting as energy and nitrogen sources and essential nutrients for amino acid auxotrophs.

In addition to the differences in nutrient composition, the IF-P group exhibited a profound reduction (33%) in visceral fat 15 . This reduction is significant because visceral fat is highly correlated with GM. While the specific influence of GM on fat depots in our study remains unclear, the shift in cytokine profile and metabolic pathways suggests an interaction between GM and fat metabolism. Regarding GM-host interaction, we did not detect changes in gut permeability assaying LBP. However, correlations were found with cytokines IL-4 and IL-13 and microbes Colidextribacter (negative association) and Ruminoccus gauveauii group (positive association). These associations may reflect the direct impact of the dietary intervention, yet they also hint at a deeper crosstalk within the gut-immune axis. This crosstalk is known to play a pivotal role in modulating host inflammation and influencing adipose tissue signaling pathways 42 . Furthermore, the observed microbial shifts, including changes in populations of Christensenella , suggest a nuanced role for certain microbes in regulating metabolic health. Notably, certain strains of Christensenella have been implicated in the regulation of key metabolic markers, such as glycemia and leptin levels, and in promoting hepatic fat oxidation 82 .

Our findings also underscore that GM composition plays a role in WL responsiveness during IF-P interventions. Subgroup analysis based on WL responsiveness revealed significant differences in species composition at the taxonomic level. The High-responder group showed an increased abundance of certain bacteria associated with metabolic benefits and anti-inflammatory effects. In contrast, the Low-responder group exhibited an increased abundance of butyrate-producing and nutritionally adaptive species (e.g., Eubacterium ventriosum 71 and Roseburia inulinivorans 72 ). Fecal metabolome analysis further highlighted differences between the two subgroups, with distinct metabolic signatures and enrichment in specific metabolic pathways. Notably, the High WL responders displayed enrichment of fecal metabolites involved in lipid metabolism. In contrast, Low responders were more prominent in pathways related to the metabolism of amino acids and peptides, including glycine, serine, and threonine, d-glutamine, and d-glutamate, as well as tyrosine metabolism and arginine biosynthesis. The latter metabolic signature has been reported in individuals with severe obesity undergoing high-protein, low-calorie diets 83 . As both High and Low WL responders were consuming the same diet, our results suggest differences in GM composition and metabolism, which could play a role in determining the success of an IF-P regimen. Though, as these enrichment analyses were performed in an exploratory manner, we acknowledge the need for a more systematic approach to validate these findings.

Finally, we provide evidence of long-term GM stabilization from these changes by following one individual over 12 months. Dietary restriction is widely used to reduce fat mass and weight in individuals with or without obesity; however, weight regain after such periods presents a critical challenge, and the underlying homeostatic mechanisms remain largely elusive. Notably, keystone taxa that became more prominent over time were associated with anti-adipogenesis, improved insulin sensitivity, and reduced metabolic disease risk. The microbial shifts were accompanied by noticeable changes in the fecal metabolome, with shifts in various metabolites and chemical subclasses. Pathway analysis identified impacts on primary bile acid biosynthesis, cysteine and methionine metabolism, and other fat mobilization and metabolic improvement pathways. These shifts were accompanied by noticeable changes in the fecal metabolome, particularly in metabolites and chemical subclasses related to lipid metabolism, nucleotide turnover, and aromatic amino acid formation.

Despite the valuable insights from our study on the complex interactions between intermittent fasting, higher protein intake using protein pacing, the GM, and circulating metabolites in obese individuals, several limitations should be acknowledged. First, our reliance on fecal samples to represent the GM may have overlooked potential microbial populations in the upper GI tract. Including samples from proximal regions in future studies would provide a more comprehensive understanding of the gut microbiome’s response to IF-P and CR. In addition, the sample size for our study was determined based on the primary outcomes related to body weight and composition from the parent study 15 . This sample size may have reduced statistical power and potentially amplified individual variability among participants. However, it is important to note that the smaller RCT design allowed for more precise control over diet and lifestyle factors, minimizing potential confounding influences on the study outcomes. Furthermore, the study’s duration was limited to eight weeks, which prevented potential insights into the differential long-term effects between the two interventions. However, we were able to extend the follow-up duration and conduct periodic assessments for a year in our case-study participant, offering a more comprehensive understanding of the sustainability of the observed changes and the potential for weight regain for IF-P. The current study compared a combination of whole food and supplements (shakes and bars; IF-P) versus primarily whole food (CR), which together with variations in protein and fiber content and type may have influenced the gut symptomatology and nutrient absorption between groups. Additionally, study participants self-reported dietary intake daily, although there was close monitoring of intake through the return of empty food packaging/containers of consumed food and daily monitoring by investigators and weekly meetings with a registered dietitian. Overall, knowledge gaps are present in this research, including how the microbiome is rebuilt after food reintroduction and how overall caloric restriction and specific macronutrients contribute to this process. However, considering the multifactorial nature of weight loss and metabolic health, our work represents an important precedent for future work. Future investigators should consider integrating these factors to provide a more comprehensive understanding of the underlying mechanisms. Additional research is warranted to characterize the metabolic signature of IF-P, the time relationship between these fasting periods, and the analysis of these metabolic changes. A strength of our High-Low-responder and case-study analyses is the hypothesis-driving nature of the findings, from which targeted microbiome and/or precision nutrition interventions can be designed and tested.

In conclusion, our study provides valuable insights into the complex interactions among intermittent fasting and protein pacing, the GM, and circulating metabolites in individuals with obesity. Specifically, intermittent fasting - protein pacing significantly reduces gut symptomatology and increases gut microbes associated with a lean phenotype ( Christensenella ) and circulating cytokines mediating total body weight and fat loss. These findings highlight the importance of personalized approaches in tailoring dietary interventions for optimal weight management and metabolic health outcomes. Further research is necessary to elucidate the underlying mechanisms driving these associations and to explore the therapeutic implications for developing personalized strategies in obesity management. Additionally, future studies should consider investigating microbial populations in upper GI sections and potential intestinal tissue remodeling to gain a more comprehensive understanding of the gut microbiome’s role in these interventions.

Study design and participants

The protocol of the clinical trial was registered on March 6, 2020 (Clinicaltrials.gov; NCT04327141), and the results of the primary analysis have been published previously 15 . Briefly, participants were recruited from Saratoga Springs, NY, and were provided informed written consent in accordance with the Skidmore College Human Subjects Institutional Review Board before participation (IRB#: 1911-859), including consent for the use of samples and data from the current study. Each procedure performed was in adherence with New York state regulations and the Federal Wide Assurance, which follows the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and in agreement with the Helsinki Declaration (revised in 1983). Their physicians performed a comprehensive medical examination/history assessment to rule out any current cardiovascular or metabolic disease. For at least six months before the start of the study, all eligible participants were either sedentary or lightly active (<30 min, two days/week of organized physical activity), with overweight or obesity (BMI > 27.5 kg/m2; % body fat > 30%), weight stable (±2 kg), and middle-aged (30–65 years). In addition, participants taking antibiotics, antifungals, or probiotics within the previous two months were excluded. Enrolled participants were matched for body weight, BMI, and body fat and randomly assigned to one of two groups: (a) IF-P ( n  = 21; 14 women; 7 men) or (b) CR ( n  = 20; 12 women; 8 men) for eight weeks. During a one-week run-in period, subjects maintained a stable body weight by consuming a similar caloric intake as their pre-enrollment caloric intake while maintaining their sedentary lifestyle. This was confirmed by matching their pre-enrollment dietary intake to the one-week run-in diet period 15 . Following baseline testing, participants were provided detailed instructions on their weight loss dietary regimen (Supplementary Table  S1 ) and received weekly dietary counseling and compliance/adherence monitoring from the research team via daily food records, and weekly registered dietitian meetings, along with weekly visits to the Human Nutrition and Metabolism laboratory at Skidmore College (Saratoga Springs, NY) for meal distribution and empty packet/container returns. All outcome variables were assessed pre (week 0), mid (week 4), and post (week 8). All participants were compensated $100 for successful completion of the study and received an additional monthly stipend of $75 for groceries (CR group only) or up to two meals per day of food supplements and meal replacements (IF-P only).

IF days consisted of ~350–550 kcals per day, in which participants were provided a variety of supplements and snacks. Protein pacing (P) days for IF-P consisted of four and five meals/day for women and men, respectively, two of which (breakfast and one other meal) were liquid meal replacement shakes with added whole foods (Whole Blend IsaLean® Shakes, 350/400 kcals, 30/36 g of protein/meal, 9 g of fiber); a whole food evening dinner meal (450/500 kcals men), an afternoon snack (200 kcals, men only), and an evening protein snack (IsaLean® or IsaPro® Shake or IsaLean Whole Blend® Bar; 200–250 kcals). This dietary regimen provided 1350–1500 and 1700–1850 kcals/day for women and men, respectively, and a macronutrient distribution targeting 35% protein, 35% carbohydrate, 20–30 g/day of fiber, and 30% fat. Isagenix International, LLC (Gilbert, AZ, USA) provided all meal replacement shakes, bars, beverages, and supplements. In comparison, participants assigned to the CR diet followed specific guidelines of the National Cholesterol Education Program Therapeutics Lifestyle Changes (TLC) diet of the American Heart Association with a strong Mediterranean diet influence of a variety of fresh vegetables, fruits, nuts, and legumes. The specific macronutrient distribution recommended was <35% of kcal as fat; 50%–60% of kcal as carbohydrates; 15% kcal as protein; <200 mg/dL of dietary cholesterol; and 20–30 g/day of fiber. The total calorie intake was 1200 and 1500 calories per day for women and men, respectively, during the 8-week weight loss intervention. In addition to weekly meetings with the registered dietitian and daily contact with research team members, subjects were provided detailed written instructions for their meal plans. They were closely monitored through daily participant-researcher communication (e.g., email, text, and mobile phone), two-day food diary analysis, weekly dietary intake journal inspections, weekly meal/supplement container distribution, and returning empty packets and containers.

Gastrointestinal (GI) symptom rating scale

Participants completed the 15-question GI symptom rating scale (GSRS) 84 at baseline, week four, and week eight. Briefly, each question is rated on a 7-point Likert scale (1 = absent; 2 = minor; 3 = mild; 4 = moderate; 5 = moderately severe; 6 = severe and 7 = very severe) and recalled from the previous week. Questions include symptoms related to upper abdominal pain, heartburn, regurgitation (acid reflux), empty feeling in the stomach, nausea, abdominal rumbling, bloating, belching, flatulence, and questions on defecation. The GSRS questionnaire provides explanations of each symptom, is understandable, and has reproducibility for measuring the presence of GI symptoms 85 . In our analysis, a score of ≥2 (minor) was defined as symptom presence, and a score ≥ 4 (moderate) was defined as moderate symptom presence. Furthermore, to better categorize symptom location, bloating, flatulence, constipation, diarrhea, stool consistency, defecation urgency, and sensation of not completely emptying bowels were classified as lower GI symptoms, and nausea, heartburn, regurgitation, upper abdominal pain, empty feeling in the stomach, stomach rumbling, and belching was classified as upper GI symptoms. Total scores were also generated for overall symptom and moderate symptom presence.

Fecal sample collection and DNA extraction

Participants were instructed to provide stool samples at baseline, week four, and week eight of the intervention. The case-study participant additionally provided samples at weeks 12, 16, 32, and 52. The entire bowel movement was collected and transported within 24 h of defecation to the Skidmore College Human Nutrition and Metabolism (Saratoga Springs, NY) laboratory using a cooler and ice packs and frozen at −80 °C. Samples were then sent to ASU (Phoenix, AZ) overnight on dry ice for analysis, where they were thawed at 4 °C and processed. Wet weight was recorded to the nearest 0.01 g after subtracting the weight of fecal collection materials. Stool samples were then rated according to the BSS 86 , homogenized in a stomacher bag, and the pH was measured (Symphony SB70P, VWR International, LLC., Radnor, PA, USA). Next, the extraction of DNA was performed using the DNeasy PowerSoil Pro Kit (Cat. No. 47016, Qiagen, Germantown, MD) per the manufacturer’s instructions. DNA concentration and quality were quantified using the NanoDrop™ OneC Microvolume UV-Vis Spectrophotometer (Thermo Scientific™, Waltham, MA) according to manufacturer instructions. The OD 260 /OD 280 ratio of all samples was ≥1.80 (demonstrating DNA purity).

Quantification of bacterial 16S rRNA genes

To estimate total bacterial biomass per sample (16S rRNA gene copies per gram of wet stool), DNA extracted from the fecal collections was assessed via quantitative polymerase chain reaction (qPCR) based on previously published methods 87 , 88 . Briefly, all 20 μL qPCR reactions contained 10 uL of 2X SYBR Premix Ex Taq ™ (Tli RNase H Plus) (Takara Bio USA, Inc., San Jose, CA, USA), 0.3 μM (0.6 μL) of each primer (926 F: AAACTCAAAKGAATTGACGG; 1062 R: CTCACRRCACGAGCTGAC), 2 μL DNA template (or PCR-grade water as negative control), and 6.8 μL nuclease-free water (Thermo Fisher Scientific, Waltham, MA, USA). PCR thermal cycling conditions were as follows: 95 °C for 5 min, followed by 35 cycles of 95 °C for 15 s, 61.5 °C for 15 s, and 72 °C for 20 s, then hold at 72 °C for 5 min, along with a melt curve of 95 °C for 15 s, 60 °C for 1 min, then 95 °C for 1 s. Quantification was performed using a QuantStudio3™ Real-Time PCR System by Applied Biosystems with QuantStudio Design and Analysis Software 1.2 from Thermo Fisher Scientific (Waltham, MA, USA). All samples were analyzed in technical replicates. For quality assurance and quality control, molecular negative template controls (NTC) consisting of PCR-grade water (Invitrogen, Waltham, MA, USA) and positive controls created by linearized plasmids were run on every qPCR plate. Standard curves were run-in triplicate and used for sample quantification, ranging from 10 7 to 10 1 copies/μL with a cycle threshold (CT) detection limit cutoff of 33. Reaction efficiency was approximately 101%, with a slope of −3.29 and R 2  ≥ 0.99.

Fecal microbiome analysis

Amplification of the 16S rRNA gene sequence was completed in triplicate PCRs using 96-well plates. Barcoded universal forward 515 F primers and 806 R reverse primers containing Illumina adapter sequences, which target the highly conserved V4 region, were used to amplify microbial DNA 89 , 90 . PCR, amplicon cleaning, and quantification were performed as previously outlined 90 . Equimolar ratios of amplicons from individual samples were pooled together before sequencing on the Illumina platform (Illumina MiSeq instrument, Illumina, Inc., San Diego, CA). Raw Illumina microbial data were cleaned by removing short and long sequences, sequences with primer mismatches, uncorrectable barcodes, and ambiguous bases using the Quantitative Insights into Microbial Ecology 2 (QIIME2) software, version 2021.8 91 .

16S rRNA sequencing produced 7,366,128 reads with a median of 53,776 per sample (range: 9512–470,848). Paired-end, demultiplexed data were imported and analyzed using QIIME2 software. Upon examination of sequence quality plots, base pairs were trimmed at position 20 and truncated at position 240 and were run through DADA2 to remove low-quality regions and construct a feature table using ASVs. Next, the ASV feature table was passed through the feature-classifier plugin 92 , which was implemented using a naive Bayes machine-learning classifier, pre-trained to discern taxonomy mapped to the latest version of the rRNA database SILVA (138.1; 99% ASVs from 515 F/806 R region of sequences) 93 . Based on an assessment of alpha rarefaction, a threshold of 6500 sequences/sample was established, retaining all samples for downstream analysis. A phylogenic tree was then constructed using the fragment-insertion plugin with SILVA at a p-sampling depth of the rarefaction threshold to impute high-quality reads and normalize for uneven sequencing depth between samples 94 . Alpha diversity (intra-community diversity) was measured using observed ASVs and the Phylogenetic diversity index. Additionally, the Shannon index was calculated for the subgroup and case-study analyses to capture richness and evenness at the species level. Beta diversity (inter-community diversity) was measured using Bray-Curtis dissimilarity.

For shotgun metagenomics, DNA was sequenced on the Illumina NextSeq 500 platform (Illumina, CA, USA) to generate 2 × 150 bp paired-end reads at greater sequencing depth with a minimum of 10 million reads. Raw Illumina sequencing reads underwent standard quality control with FastQC. Adapters were trimmed using TrimGalore. DNA sequences were aligned to Hg38 using bowtie2 95 . DNA sequences were then analyzed via the bio bakery pipeline 96 for taxonomic composition and potential functional content with MetaPhlAn4 and HUMAnN 3.0 (UniRef90 gene-families and MetaCyc metabolic pathways), using standard parameters. Functional profiling resulted in 8528 distinct Kyoto Encyclopedia of Genes and Genomes Orthology (KO) groups and 511 metabolic pathways, which align with previous human gut microbiome studies 96 .

Blood sample collection and biochemical analyses

All participants were tested between the hours of 6:00 a.m. and 9:00 a.m., after an overnight fast for body composition assessments (height, body weight, and total body composition) at weeks 0, 4, and 8. 12-h fasted venous blood samples (~20 mL) were collected into EDTA-coated vacutainer tubes and centrifuged (Hettich Rotina 46R5) for 15 min at 4000 ×  g at −4 °C. After separation, plasma was stored at −80 °C until analyzed. Undiluted plasma samples were sent to Eve Technologies (Calgary, Alberta, Canada) for assessment of inflammatory cytokines [Granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon-γ (IFNγ), interleukin (IL)-β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, and Tumor necrosis factor-α (TNFα)] using a high human sensitivity 14-plex cytokine assay (Millipore, Burlington, MA). Circulating LBP concentrations were quantified in duplicate using 1000x diluted plasma samples. A commercially available kit was used per the manufacturer’s protocol (Cat No. EH297RB, Thermo Fisher Scientific, Inc, Waltham, MA; intra-assay coefficient variation [CV] <10%).

Targeted plasma metabolomic analysis

For the plasma metabolomic analysis, a 12-h fasted venous blood sample (~20 mL) was collected into EDTA-coated vacutainer tubes and centrifuged (Hettich Rotina 46R5) for 15 min at 4000 ×  g at 4 °C. After separation, 2 mL of plasma was aliquoted and stored at −80 °C at the Biochemistry Laboratory at Skidmore College (Saratoga Springs, NY, USA). Samples were then sent to the Arizona Metabolomics Laboratory at ASU (Phoenix, AZ, USA) overnight on dry ice for analysis, where they were thawed at 4 °C and processed. Briefly, 50 μL of plasma from each sample was processed to precipitate proteins and extract metabolites by adding 500 μL MeOH and 50 μL internal standard solution (containing 1810.5 μM 13 C 3 -lactate and 142 μM 13 C 5 -glutamic acid). The mixture was vortexed (10 s) and stored for 30 min at –20 °C, then centrifuged at 224,000 ×  g for 10 min at 4 °C. Supernatants (450 μL) were extracted, transferred to new Eppendorf vials, and dried (CentriVap Concentrator; Labconco, Fort Scott, KS, USA). Samples were then reconstituted in 150 μL of 40% phosphate-buffered saline (PBS)/60% acetonitrile (ACN) and centrifuged again at 22,000 ×  g at 4 °C for 10 min. Supernatants (100 µL) were transferred to an LC autosampler vial for subsequent analysis. Quality control (QC) was performed by creating a pooled sample from all plasma samples and injecting once every ten experimental samples to monitor system performance.

The highly-reproducible targeted LC–MS/MS method used in the current investigation was modeled after previous studies 97 , 98 , 99 . The specific metabolites included in our targeted detection panel are representative of more than 35 biological pathways most essential to biological metabolism and have been successfully leveraged for the sensitive and broad detection of effects related to diet 100 , diseases 101 , drug treatment 102 , environmental contamination 103 , and lifestyle factors 104 . Briefly, LC–MS/MS experiments were performed on an Agilent 1290 UPLC-6490 QQQ-MS system (Santa Clara, CA, USA). Each sample was injected twice for analysis, 10 µL using negative and 4 µL using positive ionization modes. Chromatographic separations were performed in hydrophilic interaction chromatography (HILIC) mode on a Waters Xbridge BEH Amide column (150 × 2.1 mm, 2.5 µm particle size, Waters Corporation, Milford, MA, USA). The flow rate was 0.3 mL/min, the autosampler temperature was maintained at 4 °C, and the column compartment was set at 40 °C. The mobile phase system was composed of Solvents A (10 mM ammonium acetate, 10 mM ammonium hydroxide in 95% H 2 O/5% ACN) and B (10 mM ammonium acetate, 10 mM ammonium hydroxide in 95% ACN/5% H 2 O). After the initial 1 min isocratic elution of 90% Solvent B, the percentage of Solvent B decreased to 40% at t  = 11 min. The composition of Solvent B was maintained at 40% for 4 min ( t  = 15 min).

The mass spectrometer was equipped with an electrospray ionization (ESI) source. Targeted data acquisition was performed in multiple-reaction monitoring (MRM) mode. The LC–MS system was controlled by Agilent MassHunter Workstation software (Santa Clara, CA, USA), and extracted MRM peaks were integrated using Agilent MassHunter Quantitative Data Analysis software (Santa Clara, CA, USA).

GC–MS fecal short-chain fatty acid analysis

Before GC–MS analysis of SCFAs, frozen fecal samples were first thawed overnight under 4 °C. Then, 20 mg of each sample was homogenized with 5 μL hexanoic acid—6,6,6-d 3 (internal standard; 200 µM in H 2 O), 15 μL sodium hydroxide (NaOH [0.5 M]), and 500 μL MeOH. Samples were stored at −20 °C for 20 min and centrifuged at 22,000 ×  g for 10 min afterward. Next, 450 μL of supernatant was collected, and the sample pH was adjusted to 10 by adding 30 μL of NaOH:H 2 O (1:4, v-v). Samples were then dried, and the residues were initially derivatized with 40 µL of 20 mg/mL MeOX solution in pyridine under 60 °C for 90 min. Subsequently, 60 µL of MTBSTFA containing d 27 -mysristic acid was added, and the mixture was incubated at 60 °C for 30 min. The samples were then vortexed for 30 s and centrifuged at 22,000 ×  g for 10 min. Finally, 70 µL of supernatant was collected from each sample and injected into new glass vials for GC–MS analysis.

GC–MS conditions used here were adopted from a previously published protocol 105 . Briefly, GC–MS experiments were performed on an Agilent 7820 A GC-5977B MSD system (Santa Clara, CA); all samples were analyzed by injecting 1 µL of prepared samples. Helium was the carrier gas with a constant flow rate of 1.2 mL/min. Separation of metabolites was achieved using an Agilent HP-5 ms capillary column (30 m × 250 µm × 0.25 µm). Ramping parameters were as follows: column temperature was maintained at 60 °C for 1 min, increased at a rate of 10 °C/min to 325 °C, and then held at this temperature for 10 min. Mass spectral signals were recorded at an m/z range of 50–600, and data extraction was performed using Agilent Quantitative Analysis software. Following peak integration, metabolites were filtered for reliability. Only those with QC CV < 20% and a relative abundance of 1000 in > 80% of samples were retained for statistical analysis.

Untargeted fecal metabolomic analysis

Briefly, each fecal sample (~20 mg) was homogenized in 200 µL MeOH:PBS (4:1, v-v, containing 1810.5 μM 13 C 3 -lactate and 142 μM 13 C 5 -glutamic Acid) in an Eppendorf tube using a Bullet Blender homogenizer (Next Advance, Averill Park, NY). Then 800 µL MeOH:PBS (4:1, v-v, containing 1810.5 μM 13 C 3 -lactate and 142 μM 13 C 5 -glutamic Acid) was added, and after vortexing for 10 s, the samples were stored at −20 °C for 30 min. The samples were then sonicated in an ice bath for 30 min. The samples were centrifuged at 22,000 ×  g for 10 min (4 °C), and 800 µL supernatant was transferred to a new Eppendorf tube. The samples were then dried under vacuum using a CentriVap Concentrator (Labconco, Fort Scott, KS). Prior to MS analysis, the obtained residue was reconstituted in 150 μL 40% PBS/60% ACN. A quality control (QC) sample was pooled from all the study samples.

The untargeted LC–MS metabolomics method used here was modeled after that developed and used in a growing number of studies 106 , 107 , 108 . Briefly, all LC–MS experiments were performed on a Thermo Vanquish UPLC-Exploris 240 Orbitrap MS instrument (Waltham, MA). Each sample was injected twice, 10 µL for analysis using negative ionization mode and 4 µL for analysis using positive ionization mode. Both chromatographic separations were performed in hydrophilic interaction chromatography (HILIC) mode on a Waters XBridge BEH Amide column (150 × 2.1 mm, 2.5 µm particle size, Waters Corporation, Milford, MA). The flow rate was 0.3 mL/min, autosampler temperature was kept at 4 °C, and the column compartment was set at 40 °C. The mobile phase was composed of Solvents A (10 mM ammonium acetate, 10 mM ammonium hydroxide in 95% H 2 O/5% ACN) and B (10 mM ammonium acetate, 10 mM ammonium hydroxide in 95% ACN/5% H 2 O). After the initial 1 min isocratic elution of 90% B, the percentage of Solvent B decreased to 40% at t  = 11 min. The composition of Solvent B maintained at 40% for 4 min ( t  = 15 min), and then the percentage of B gradually went back to 90%, to prepare for the next injection. Using mass spectrometer equipped with an electrospray ionization (ESI) source, we collected untargeted data from 70 to 1050 m/z.

To identify peaks from the MS spectra, we made extensive use of the in-house chemical standards (~600 aqueous metabolites), and in addition, we searched the resulting MS spectra against the HMDB library, Lipidmap database, METLIN database, as well as commercial databases including mzCloud, Metabolika, and ChemSpider. The absolute intensity threshold for the MS data extraction was 1000, and the mass accuracy limit was set to 5 ppm. Identifications and annotations used available data for retention time (RT), exact mass (MS), MS/MS fragmentation pattern, and isotopic pattern. We used the Thermo Compound Discoverer 3.3 software for aqueous metabolomics data processing. The untargeted data were processed by the software for peak picking, alignment, and normalization. To improve rigor, only the signals/peaks with CV < 20% across quality control (QC) pools, and the signals showing up in >80% of all the samples were included for further analysis. To ensure the robustness of our model validation, we employed an enhanced validation approach by repeating the LOOCV process 100 times. Each iteration involves excluding one sample from the dataset to serve as the test set, with the model being trained on the remaining samples. This approach, referred to as ‘repeated LOOCV’, was adopted to mitigate bias and provide a thorough validation of our model’s predictive capability. The method signifies the number of repetitions of the LOOCV process, rather than splitting the dataset into 100 equal parts.

Multi-omics data analysis

For MOFA, bacterial 16S rRNA ASVs and plasma metabolites were integrated using the MOFA2 package 55 . Before integration, ASV sequences were filtered (minimum of 5 ASV in greater than 10% of all samples), collapsed to the genus level, and scaled using a centralized-log-ratio, as described previously 109 . Plasma metabolites were scaled and normalized as described in the metabolome analysis. The inputs for MOFA model training comprised 53 taxa and 138 metabolites. The latent factors and feature loadings were extracted from the best-trained model with the built-in functions of MOFA2. After model fitting, the number of factors was estimated by requiring a minimum of 2% variance explained across all microbiome modalities.

Integrating microbial taxa with the same filtration as stated above (at the genus level from 16S amplicon sequencing and species level from metagenomic sequencing) and cytokine data and fecal metabolomic data, respectively, was conducted with GFLASSO (R package: GFLASSO, v0.0.0.9000). This correlation-based network solution can handle multiple response variables for a given set of predictors (in this case: 1. cytokine abundances predicted by microbial taxa response; and 2. fecal metabolite response predicted by microbial taxa). Solution parsimony was determined by an unweighted (i.e., presence or absence of association by imposing a correlation threshold) network structure. The regularization and fusion parameters were determined from the smallest root mean squared error (RMSE) estimate via cross-validation, accounting for interdependencies among microbial features. The tested parameters encompassed all combinations between λ and γ with values ranging from 0 to 1 (inclusive) in step increments of 0.1. GFLASSO coefficient matrices were constructed using a threshold coefficient of >0.02 to discern the strongest associative signals.

Statistical analysis

Gastrointestinal symptom scores were on the low end of the GSRS scale and not normally distributed; therefore, nonparametric statistical tests were applied. Symptom prevalence (number of scores ≥ 2) and moderate symptom prevalence (≥4) for total, upper, and lower GI GSRS clusters were analyzed using contingency tables. Specifically, differences between IF-P and CR GI symptoms at baseline were compared using a Fisher’s Exact test, whereas baseline vs. weeks four and eight values were compared with McNemar’s test. Stool weight, BSS, fecal pH, plasma cytokines and LBP, and SCFAs were assessed for normality with Q-Q plots and Shapiro-Wilk tests and log-transformed where appropriate. These were then tested for time and interaction (group × time) effects using linear-mixed effect (LME) models, with each participant included as a random effect.

For analysis and visualization of the microbiome data, artifacts generated in QIIME2 were imported into the R environment (v4.2.2) using the phyloseq package (v1.42.0) 110 . Before conducting downstream analyses, sequences were filtered to remove all non-bacterial sequences, including archaea, mitochondria, and chloroplasts. After assessing normality (Shapiro-Wilk’s tests), LME models were used to test the effect of time and the interaction of group and time with the covariates of age and sex with each participant included as a random effect on the alpha diversity metrics using the nLME package (v3.1.160). For beta diversity, a nested permutational analysis of variance (PERMANOVA) was conducted on Bray-Curtis dissimilarities using the Adonis test in the vegan package (v2.6.2) with 999 permutations. The PERMANOVA model incorporated the factors of time, individual, interaction (group × time), and participant (nested factor). A permutation test for homogeneity in multivariate dispersion (PERMDISP) was conducted using the ‘betadisper’ function in the vegan package to compare dispersion. To support the Adonis analysis, intra-individual differences were also compared between groups, as previously described 111 , by calculating the within-subject distance for paired samples (baseline vs. weeks four and eight) and testing for group distances (Wilcoxon rank-sum test). Differential abundance analysis was performed using MaAsLin2 (v1.12.0) 18 . To detect changes in microbial features between groups over time, we built linear-mixed models that include group, time, and their interaction, with age and sex as covariates and the participant as a random factor. Before analysis, raw counts from the ASV table were filtered for any sequence not present five times in at least 30% of all samples. A significant p-value for the product term indicates that changes in microbial features differed over time between groups. The Benjamini–Hochberg (BH) procedure was used to correct for multiple testing at ≤0.10. To assess the correlation between changes in specific taxa and biomarkers over the eight-week intervention, Spearman correlation tests were performed.

Univariate and multivariate analyses of plasma metabolites and metabolic ontology analysis were performed, and results were visualized using the MetaboAnalystR 5.0 112 . Human metabolomic data were mapped to the Kyoto Encyclopedia of Genes and Genomes (KEGG) human pathway library to analyze predicted states 113 . The data were log 10 -transformed, and Pareto scaled to approximate normality before all analyses. A GLM was constructed with age, sex, and time as covariates to determine significantly affected metabolites by group intervention. Levene’s test was performed to detect significant homogeneity. The BH procedure was used to correct for multiple testing at ≤0.10. Fecal metabolomic analysis for the subgroup comparison was performed by assessing logFC values between groups with a Wilcoxon rank-sum test with BH adjustment. For pathway analysis, the impact was calculated using a hypergeometric test, while significance was determined using a test of relative betweenness centrality. Importantly, the BH procedure was not applied to pathway and enzyme enrichment analyses for the subgroup assessment since these analyses involve testing the significance of multiple related hypotheses rather than independent hypotheses, which is too conservative, resulting in false negative results.

For MOFA, latent factors explaining ≥2.0% of model variance from the plasma metabolomic and amplicon microbiome data were used to perform Spearman correlations on anthropometric and nutritional data and compared between IF-P and CR groups using Wilcoxon rank-sum tests. The highest beta coefficients (>0.3) detected from GFLASSO models were further assessed by performing Spearman correlations of select microbial features with the response variables (i.e., cytokines and fecal metabolites). All statistical tests were performed with a significance level of p  < 0.05 and BH correction of p .adj < 0.10. In addition, we present data in this study in accordance with the ‘Strengthening The Organization and Reporting of Microbiome Studies’ (STORMS) guidelines for human microbiome research 114 .

Reporting summary

Further information on research design is available in the  Nature Portfolio Reporting Summary linked to this article.

Data availability

The microbiome sequencing data generated in this study have been deposited in the BioProject Database of National Centre for Biotechnology Information database under accession code PRJNA847971 . The metadata data linking the microbiome sequences with the appropriate sample ID and intervention in this study are provided in Supplementary Data  1 . The processed data are available at https://github.com/Alex-E-Mohr/GM-Remodeling-IF-ProteinPacing-vs-CaloricRestriction .  Source data are provided with this paper.

Code availability

The R code used for analysis and figure generation for reproducibility purposes are available at: https://github.com/Alex-E-Mohr/GM-Remodeling-IF-ProteinPacing-vs-CaloricRestriction . 115

Asnicar, F. et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat. Med. 27 , 321–332 (2021).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Li, M. et al. Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice. Nat. Commun. 13 , 2060 (2022).

Article   ADS   CAS   PubMed   PubMed Central   Google Scholar  

Machado, A. C. D. et al. Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome. Cell Rep. 40 , 111008 (2022).

Article   PubMed Central   Google Scholar  

von Schwartzenberg R.J. et al. Caloric restriction disrupts the microbiota and colonization resistance. Nature 595 , 272–277 (2021).

Maifeld, A. et al. Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. Nat. Commun. 12 , 1970 (2021).

Corbin, K. D. et al. Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial. Nat. Commun. 14 , 3161 (2023).

Arciero, P. J. et al. Increased protein intake and meal frequency reduces abdominal fat during energy balance and energy deficit. Obesity 21 , 1357–1366 (2013).

Article   CAS   PubMed   Google Scholar  

Arciero, P. J. et al. Protein-pacing caloric-restriction enhances body composition similarly in obese men and women during weight loss and sustains efficacy during long-term weight maintenance. Nutrients 8 , 476 (2016).

Article   PubMed   PubMed Central   Google Scholar  

Mohr, A. E. et al. Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity. Front. Nutr. 9 , 1036080 (2022).

He, F., Zuo, L., Ward, E. & Arciero, P. J. Serum polychlorinated biphenyls increase and oxidative stress decreases with a protein-pacing caloric restriction diet in obese men and women. Int. J. Environ. Res. Public Health 14 , 59 (2017).

Ives, S. J. et al. Multi-modal exercise training and protein-pacing enhances physical performance adaptations independent of growth hormone and BDNF but may be dependent on IGF-1 in exercise-trained men. Growth Horm. IGF Res. 32 , 60–70 (2017).

Zuo, L. et al. Comparison of high-protein, intermittent fasting low-calorie diet and heart healthy diet for vascular health of the obese. Front. Physiol. 7 , 350 (2016).

Article   ADS   PubMed   PubMed Central   Google Scholar  

Zhong, W. et al. High-protein diet prevents fat mass increase after dieting by counteracting Lactobacillus-enhanced lipid absorption. Nat. Metab. 4 , 1713–1731 (2022).

U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025 , 9th edn DietaryGuidelines.gov (2020).

Arciero, P. J. et al. Intermittent fasting and protein pacing are superior to caloric restriction for weight and visceral fat loss. Obesity 31 , 139–149 (2023).

Lichtenstein, A. H. et al. 2021 Dietary guidance to improve cardiovascular health: a scientific statement from the american heart association. Circulation 144 , e472–e487 (2021).

Article   PubMed   Google Scholar  

Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352 , 560–564 (2016).

Article   ADS   CAS   PubMed   Google Scholar  

Mallick, H. et al. Multivariable association discovery in population-scale meta-omics studies. PLos Comput. Biol. 17 , e1009442 (2021).

Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489 , 220–230 (2012).

Waters, J. L. & Ley, R. E. The human gut bacteria Christensenellaceae are widespread, heritable, and associated with health. BMC Biol. 17 , 83 (2019).

Beaumont, M. et al. Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans. Am. J. Clin. Nutr. 106 , 1005–1019 (2017).

Tavella, T. et al. Elevated gut microbiome abundance of Christensenellaceae, Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly. Gut Microbes 13 , 1880221 (2021).

Bischoff, S. C. et al. Gut microbiota patterns predicting long-term weight loss success in individuals with obesity undergoing nonsurgical therapy. Nutrients 14 , 3182 (2022).

Vieira-Silva, S. et al. Species–function relationships shape ecological properties of the human gut microbiome. Nat. Microbiol. 1 , 16088 (2016).

Cummings, J. H. & Macfarlane, G. T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70 , 443–459 (1991).

Tims, S. et al. Microbiota conservation and BMI signatures in adult monozygotic twins. ISME J. 7 , 707–717 (2013).

Atzeni, A. et al. Taxonomic and functional fecal microbiota signatures associated with insulin resistance in non-diabetic subjects with overweight/obesity within the frame of the PREDIMED-plus study. Front. Endocrinol. 13 , 804455 (2022).

Article   Google Scholar  

Oliver, A. et al. High-fiber, whole-food dietary intervention alters the human gut microbiome but not fecal short-chain fatty acids. Msystems 6 , e00115–e00121 (2021).

McOrist, A. L. et al. Fecal butyrate levels vary widely among individuals but are usually increased by a diet high in resistant starch. J. Nutr. 141 , 883–889 (2011).

Bendiks, Z. A., Knudsen, K. E. B., Keenan, M. J. & Marco, M. L. Conserved and variable responses of the gut microbiome to resistant starch type 2. Nutr. Res. 77 , 12–28 (2020).

Boulangé, C. L., Neves, A. L., Chilloux, J., Nicholson, J. K. & Dumas, M.-E. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med 8 , 42 (2016).

Shiau, M.-Y. et al. Mechanism of interleukin-4 reducing lipid deposit by regulating hormone-sensitive lipase. Sci. Rep. 9 , 11974 (2019).

Bruun, J. M., Pedersen, S. B., Kristensen, K. & Richelsen, B. Opposite regulation of interleukin‐8 and tumor necrosis factor‐α by weight loss. Obes. Res. 10 , 499–506 (2002).

Steensberg, A. et al. Production of interleukin‐6 in contracting human skeletal muscles can account for the exercise‐induced increase in plasma interleukin‐6. J. Physiol. 529 , 237–242 (2000).

Hall et al. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J. Clin. Endocrinol. Metab. 88 , 3005–3010 (2003).

Wueest, S. et al. Interleukin-6 contributes to early fasting-induced free fatty acid mobilization in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 306 , R861–R867 (2014).

Wu, D. et al. Interleukin-13 (IL-13)/IL-13 receptor α1 (IL-13Rα1) signaling regulates intestinal epithelial cystic fibrosis transmembrane conductance regulator channel-dependent Cl− secretion. J. Biol. Chem. 286 , 13357–13369 (2011).

Gamage, H. K. A. H. et al. Intermittent fasting has a diet-specific impact on the gut microbiota and colonic mucin O-glycosylation of mice. Preprint at bioRxiv https://doi.org/10.1101/2022.09.15.508181 (2022).

Song, E.-J., Shin, N. R., Jeon, S., Nam, Y.-D. & Kim, H. Lorcaserin and phentermine exert anti-obesity effects with modulation of the gut microbiota. Front. Microbiol. 13 , 1109651 (2023).

Wang, M. et al. Olive fruit extracts supplement improve antioxidant capacity via altering colonic microbiota composition in mice. Front. Nutr. 8 , 645099 (2021).

Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464 , 59–65 (2010).

Mohr, A. E., Crawford, M., Jasbi, P., Fessler, S. & Sweazea, K. L. Lipopolysaccharide and the gut microbiota: considering structural variation. FEBS Lett. 596 , 849–875 (2022).

Teruya, T., Chaleckis, R., Takada, J., Yanagida, M. & Kondoh, H. Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood. Sci. Rep. 9 , 854 (2019).

Collet, T.-H. et al. A metabolomic signature of acute caloric restriction. J. Clin. Endocrinol. Metab. 102 , 4486–4495 (2017).

Vázquez-Fresno, R. et al. Metabolomic pattern analysis after mediterranean diet intervention in a nondiabetic population: a 1- and 3-year follow-up in the PREDIMED study. J. Proteome Res. 14 , 531–540 (2015).

Sankaranarayanan, R., Kumar, D. R., Patel, J. & Bhat, G. J. Do aspirin and flavonoids prevent cancer through a common mechanism involving hydroxybenzoic acids?—The metabolite hypothesis. Molecules 25 , 2243 (2020).

Aon, M. A. et al. Untangling determinants of enhanced health and lifespan through a multi-omics approach in mice. Cell Metab. 32 , 100–116.e4 (2020).

Sekhar, R. V. et al. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care 34 , 162–167 (2011).

Nguyen, D., Hsu, J. W., Jahoor, F. & Sekhar, R. V. Effect of increasing glutathione with cysteine and glycine supplementation on mitochondrial fuel oxidation, insulin sensitivity, and body composition in older HIV-infected patients. J. Clin. Endocrinol. Metab. 99 , 169–177 (2014).

Chen, L. et al. Glycine transporter-1 and glycine receptor mediate the antioxidant effect of glycine in diabetic rat islets and INS-1 cells. Free Radic. Biol. Med. 123 , 53–61 (2018).

Breum, L., Rasmussen, M. H., Hilsted, J. & Fernstrom, J. D. Twenty-four–hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction 1, 2, 3. Am. J. Clin. Nutr. 77 , 1112–1118 (2003).

Fernstrom, J. D. et al. Diurnal variations in plasma concentrations of tryptophan, tryosine, and other neutral amino acids: effect of dietary protein intake. Am. J. Clin. Nutr. 32 , 1912–1922 (1979).

Chen, L. et al. Influence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolome. Nat. Med. 28 , 2333–2343 (2022).

Fan, Y. & Pedersen, O. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 19 , 55–71 (2021).

Argelaguet, R. et al. Multi‐Omics Factor Analysis—a framework for unsupervised integration of multi‐omics data sets. Mol. Syst. Biol. 14 , e8124 (2018).

Anderson, E. M. et al. Temporal dynamics of the intestinal microbiome following short-term dietary restriction. Nutrients 14 , 2785 (2022).

Gerritsen, J. et al. A comparative and functional genomics analysis of the genus Romboutsia provides insight into adaptation to an intestinal lifestyle. Preprint at bioRxiv https://doi.org/10.1101/845511 (2019).

Caldovic, L. et al. N-acetylglutamate synthase: structure, function and defects. Mol. Genet. Metab. 100 , S13–S19 (2010).

Parker, B. J., Wearsch, P. A., Veloo, A. C. M. & Rodriguez-Palacios, A. The genus Alistipes: gut bacteria with emerging implications to inflammation, cancer, and mental health. Front. Immunol. 11 , 906 (2020).

Yang, J. et al. Oscillospira - a candidate for the next-generation probiotics. Gut Microbes 13 , 1987783 (2021).

Jensen, M. D. et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults. Circulation 129 , S102–S138 (2014).

Gomez-Arango, L. F. et al. Low dietary fiber intake increases Collinsella abundance in the gut microbiota of overweight and obese pregnant women. Gut Microbes 9 , 189–201 (2018).

Chen, J. et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 8 , 43 (2016).

Astbury, S. et al. Lower gut microbiome diversity and higher abundance of proinflammatory genus Collinsella are associated with biopsy-proven nonalcoholic steatohepatitis. Gut Microbes 11 , 569–580 (2020).

Lim, R. R. X. et al. Gut microbiome responses to dietary intervention with hypocholesterolemic vegetable oils. npj Biofilms Microbiomes 8 , 24 (2022).

Atarashi, K. et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500 , 232–236 (2013).

Louis, P. & Flint, H. J. Diversity, metabolism and microbial ecology of butyrate‐producing bacteria from the human large intestine. FEMS Microbiol. Lett. 294 , 1–8 (2009).

Bui, T. P. N. et al. Mutual metabolic interactions in co-cultures of the intestinal Anaerostipes rhamnosivorans with an acetogen, methanogen, or pectin-degrader affecting butyrate production. Front. Microbiol. 10 , 2449 (2019).

Kaci, G. et al. Anti-inflammatory properties of streptococcus salivarius, a commensal bacterium of the oral cavity and digestive tract. Appl. Environ. Microbiol. 80 , 928–934 (2014).

Couvigny, B. et al. Commensal streptococcus salivarius modulates PPARγ transcriptional activity in human intestinal epithelial cells. PLoS ONE 10 , e0125371 (2015).

Barcenilla, A. et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol. 66 , 1654–1661 (2000).

Scott, K. P. et al. Substrate-driven gene expression in Roseburia inulinivorans: importance of inducible enzymes in the utilization of inulin and starch. Proc. Natl Acad. Sci. USA 108 , 4672–4679 (2011).

Hosomi, K. et al. Oral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota. Nat. Commun. 13 , 4477 (2022).

Bui, T. P. N. et al. Conversion of dietary inositol into propionate and acetate by commensal Anaerostipes associates with host health. Nat. Commun. 12 , 4798 (2021).

Zeevi, D. et al. Structural variation in the gut microbiome associates with host health. Nature 568 , 43–48 (2019).

Brahe, L. K. et al. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity. Nutr. Diabetes 5 , e159–e159 (2015).

Deaver, J. A., Eum, S. Y. & Toborek, M. Circadian disruption changes gut microbiome taxa and functional gene composition. Front Microbiol 09 , 737 (2018).

Ze, X., Duncan, S. H., Louis, P. & Flint, H. J. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon. ISME J. 6 , 1535–1543 (2012).

Ngai, P. H. K., Zhao, Z. & Ng, T. B. Agrocybin, an antifungal peptide from the edible mushroom Agrocybe cylindracea. Peptides 26 , 191–196 (2005).

Sánchez, M. et al. Modulatory effect of intestinal polyamines and trace amines on the spontaneous phasic contractions of the isolated ileum and colon rings of mice. Food Nutr. Res. 61 , 1321948 (2017).

Lassen, P. B. et al. Protein supplementation during an energy-restricted diet induces visceral fat loss and gut microbiota amino acid metabolism activation: a randomized trial. Sci. Rep. 11 , 15620 (2021).

Mazier, W. et al. A new strain of christensenella minuta as a potential biotherapy for obesity and associated metabolic diseases. Cells 10 , 823 (2021).

Salazar, N. et al. Fecal metabolome and bacterial composition in severe obesity: impact of diet and bariatric surgery. Gut Microbes 14 , 2106102 (2022).

Svedlund, J., Sjödin, I. & Dotevall, G. GSRS—clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig. Dis. Sci. 33 , 129–134 (1988).

Kulich, K. R. et al. Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health Qual. Life Out. 6 , 12 (2008).

Riegler, G. & Esposito, I. Bristol scale stool form. A still valid help in medical practice and clinical research. Tech. Coloproctol. 5 , 163–164 (2001).

Yang, Y.-W. et al. Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in mouse feces. Appl. Environ. Microbiol. 81 , 6749–6756 (2015).

Gregoris, T. B. D., Aldred, N., Clare, A. S. & Burgess, J. G. Improvement of phylum- and class-specific primers for real-time PCR quantification of bacterial taxa. J. Microbiol. Methods 86 , 351–356 (2011).

Caporaso, J. G. et al. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proc. Natl Acad. Sci. USA 108 , 4516–4522 (2010).

Caporaso, J. G. et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 6 , 1621–1624 (2012).

Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37 , 852–857 (2019).

Bokulich, N. A. et al. Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2’s q2-feature-classifier plugin. Microbiome 6 , 90 (2018).

Quast, C. et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 41 , D590–D596 (2012).

McKnight, D. T. et al. Methods for normalizing microbiome data: an ecological perspective. Methods Ecol. Evol. 10 , 389–400 (2019).

Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9 , 357–359 (2012).

Beghini, F. et al. Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. Elife 10 , e65088 (2021).

Bapat, A. et al. Hypoxia promotes erythroid differentiation through the development of progenitors and proerythroblasts. Exp. Hematol. 97 , 32–46.e35 (2021).

Jasbi, P. et al. Metabolic profiling of neocortical tissue discriminates Alzheimer’s disease from mild cognitive impairment, high pathology controls, and normal controls. J. Proteome Res. 20 , 4303–4317 (2021).

Jasbi, P. et al. Microbiome and metabolome profiles of high screen time in a cohort of healthy college students. Sci. Rep. 12 , 3452 (2022).

Basile, A. J. et al. A four-week white bread diet does not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves, Zenaida macroura. Comp. Biochem. Physiol. Part A Mol. Integr. Physiol. 247 , 110718 (2020).

Article   CAS   Google Scholar  

Johnston, C. S. et al. Daily vinegar ingestion improves depression scores and alters the metabolome in healthy adults: a randomized controlled trial. Nutrients 13 , 4020 (2021).

Gu, H., Shi, X., Jasbi, P. & Patterson, J. Viruses as therapeutics, methods and protocols. Methods Mol. Biol. 2225 , 179–197 (2020).

He, H. et al. An integrative cellular metabolomic study reveals downregulated tricarboxylic acid cycle and potential biomarkers induced by tetrabromobisphenol A in human lung A549 cells. Environ. Toxicol. 38 , 7–16 (2023).

Mohr, A. E. et al. Association of food insecurity on gut microbiome and metabolome profiles in a diverse college-based sample. Sci. Rep. 12 , 14358 (2022).

Gu, H., Jasbi, P., Patterson, J. & Jin, Y. Enhanced detection of short‐chain fatty acids using gas chromatography mass spectrometry. Curr. Protoc. 1 , e177 (2021).

Qi, Y. et al. Metabolomics study of resina draconis on myocardial ischemia rats using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with pattern recognition methods and metabolic pathway analysis. Évid. Based Complement. Altern. Med. 2013 , 438680 (2013).

Google Scholar  

Yao, W. et al. Integrated plasma and urine metabolomics coupled with HPLC/QTOF-MS and chemometric analysis on potential biomarkers in liver injury and hepatoprotective effects of Er-Zhi-Wan. Anal. Bioanal. Chem. 406 , 7367–7378 (2014).

Wei, Y. et al. Early breast cancer detection using untargeted and targeted metabolomics. J. Proteome Res. 20 , 3124–3133 (2021).

Haak, B. W. et al. Integrative transkingdom analysis of the gut microbiome in antibiotic perturbation and critical illness. mSystems 6 , e01148–20 (2021).

McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLos One 8 , e61217 (2013).

Bokulich, N. A. et al. q2-longitudinal: longitudinal and paired-sample analyses of microbiome data. Msystems 3 , e00219–18 (2018).

Pang, Z. et al. MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 49 , W388–W396 (2021).

Kanehisa, M. & Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28 , 27–30 (2000).

Mirzayi, C. et al. Reporting guidelines for human microbiome research: the STORMS checklist. Nat. Med. 27 , 1885–1892 (2021).

Mohr, A. E. et al. Gut microbiome remodeling and metabolomic profile in response to protein pacing with intermittent fasting versus continuous caloric restriction https://doi.org/10.5281/zenodo.10971120 (2024).

Download references

Acknowledgements

We thank the trial volunteers for their dedication and commitment to the study protocol. We are grateful for the research assistants from Skidmore College who provided valuable assistance with study protocol design, scheduling, recruitment, data testing, collection, entry, and statistical analysis, and preparation of manuscripts: Molly Boyce, Jenny Zhang, Melissa Haas, Olivia Furlong, Emma Valdez, Jessica Centore, Annika Smith, Kaitlyn Judd, Aaliyah Yarde, Katy Ehnstrom, Dakembay Hoyte, Sheriden Beard, Heather Mak, and Monique Dudar. We are grateful for the extensive guidance and counseling provided by the registered dietitian Jaime Martin. We thank research coordinator Michelle Poe for her superior dedication to all aspects of the study. This study was primarily funded by an unrestricted grant from Isagenix International LLC to P.J.A. (grant #:1911-859), with secondary funding provided to K.L.S.

Author information

Authors and affiliations.

College of Health Solutions, Arizona State University, Phoenix, AZ, USA

Alex E. Mohr, Karen L. Sweazea, Corrie M. Whisner, Dorothy D. Sears, Haiwei Gu & Judith Klein-Seetharaman

Biodesign Institute Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA

Alex E. Mohr, Karen L. Sweazea, Devin A. Bowes, Corrie M. Whisner & Rosa Krajmalnik-Brown

Center for Evolution and Medicine, College of Liberal Arts and Sciences, Arizona State University, Tempe, AZ, USA

Karen L. Sweazea

School of Molecular Sciences, Arizona State University, Tempe, AZ, USA

Paniz Jasbi & Judith Klein-Seetharaman

Systems Precision Engineering and Advanced Research (SPEAR), Theriome Inc., Phoenix, AZ, USA

Paniz Jasbi

Center of Translational Science, Florida International University, Port St. Lucie, FL, USA

Yan Jin & Haiwei Gu

Human Nutrition and Metabolism Laboratory, Department of Health and Human Physiological Sciences, Skidmore College, Saratoga Springs, NY, USA

Karen M. Arciero & Paul J. Arciero

Isagenix International, LLC, Gilbert, AZ, USA

Eric Gumpricht

School of Health and Rehabilitation Sciences, Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA

Paul J. Arciero

You can also search for this author in PubMed   Google Scholar

Contributions

Study conceived and designed: P.J.A. Manuscript preparation with input from all authors: A.E.M., K.L.S., D.A.B., P.J., C.M.W., D.D.S., R.K.-B., H.G., J.K.-S., K.M.A., E.G., and P.J.A. Randomized study design and execution: K.M.A., and P.J.A. Microbiome analysis: A.E.M., D.A.B., C.M.W., and R.K.-B. Blood analyte analysis: A.E.M., K.L.S., and P.J.A. Metabolomic analysis: A.E.M., Y.J., H.G., and P.J. Statistical analysis and data presentation: A.E.M., C.M.W., D.D.S., R.K.-B., and P.J.A. Supervision and funding: K.L.S., E.G., and P.J.A.

Corresponding author

Correspondence to Paul J. Arciero .

Ethics declarations

Competing interests.

P.J.A. is a consultant for Isagenix International LLC, the study’s sponsor, he is an advisory board member of the International Protein Board (iPB), and he receives financial compensation for books and keynote presentations on protein pacing ( www.paularciero.com ). Eric Gumpricht is employed by Isagenix International, LLC, the funding source for this research. Isagenix International, LLC had no role in the study design, data collection, analysis, or decision to publish. No authors have financial interests regarding the outcomes of this investigation. The other authors declare no competing interests.

Peer review

Peer review information.

Nature Communications thanks Gertrude Ecklu-Mensah, Saar Shoer, and Levi Teigen for their contribution to the peer review of this work. A peer review file is available.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information, peer review file, description of additional supplementary files, reporting summary, source data, source data, rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Cite this article.

Mohr, A.E., Sweazea, K.L., Bowes, D.A. et al. Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction. Nat Commun 15 , 4155 (2024). https://doi.org/10.1038/s41467-024-48355-5

Download citation

Received : 13 September 2023

Accepted : 26 April 2024

Published : 28 May 2024

DOI : https://doi.org/10.1038/s41467-024-48355-5

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

By submitting a comment you agree to abide by our Terms and Community Guidelines . If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.