PONE-D-24-29210Inulin promotes appetite in mice by regulating the gut microbiota under conditions of rapid entry to the plateauPLOS ONE

Dear Dr. Li,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Additional Editor Comments:

Thank you for you submission to PLOS ONE. While your manuscript has merit, the reviewer and I noted several issues that require attention to prior to consideration for approval. My additional comments are listed here with the reviewer's at the end of this letter. Overall the reviewer and I found the research interesting and valuable for PLOS ONE readers but major revisions required.

1. Additional careful proofread is required as there are spelling and grammar errors that need corrected.

2. I do not see that false discovery rate correction was performed for the microbiome evaluations - please perform statistical analysis with FDR correction.

3. Please describe in the methods how the mice were housed and in how many cages they were housed in. Caging effect may be a large confounder of the data.

4. Include dot plot graphs so that the reader and reviewer may see the individual distribution of cohort animals.

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Please submit your revised manuscript by Oct 18 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Ryan M. Thomas, MD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Editor Comments:

The manuscript presents an interesting study on the effects of inulin on appetite modulation in mice, focusing on gut microbiota changes under rapid entry to plateau conditions. The concept is well-founded, and the methodology appears robust. However, several areas require revision and clarification to enhance the manuscript's clarity and scientific rigor.

Specific Comments:

1. Introduction: The introduction should better contextualize the research within existing literature. Please expand on previous studies that have investigated the effects of inulin on gut microbiota and appetite, particularly in non-plateau conditions, to strengthen the rationale for this study.

2. Data presentation: Some figures and tables are very complex. Simplify them if possible.

3. Discussion: The discussion section needs further improvement. Explain how the results are consistent with the initial hypothesis. Discuss the implications of these findings for using inulin as a functional food, especially under the unique conditions of rapid plateau entry. The discussion should also include a section on study limitations. Address potential biases and generalizability of the results to other populations or species.

4. References: Verification and Formatting: Please review references 1 to 11 for relevance and accuracy, ensuring they are updated and formatted according to the journal’s guidelines.

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Reviewer #1: Yes:  Dr. Mai Albaik

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PONE-D-24-29210R1Inulin promotes appetite in mice by regulating the gut microbiota under conditions of rapid entry to the plateauPLOS ONE

Dear Dr. Li,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The authors have clearly addressed the comments from the first round of reviews. A second round of review suggests a minor revision is required. I also advise the authors to update the background with rescent publications that came after the original submission. 

Please submit your revised manuscript by Apr 25 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Yash Gupta, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Reviewers have raised deficiencies that are to be corrected.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: N/A

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

Reviewer #3: Present work, titled as “Inulin promotes appetite in mice by regulating the gut microbiota under conditions of rapid entry to the plateau”, by Xiaoli Li and co-workers aims to explore role of inulin, a dietary fiber, in regulating gut microbiota with a model study using fifty seven-week-old SPF-grade C57BL/6J male mice. Authors have chosen two different environmental conditions, i.e. regular and rush to plateau to study structural as well as functional characteristics of inulin uptake affecting the gut microbiota. Results demonstrate that inulin has a direct impact on metabolism and secretion of appetite hormones which result in enhanced appetite and body weight by increasing useful gut bacteria.

Authors have systematically introduced the concepts involved in developing the study of inulin in the context of plateau health supplements along with detailed methodology adopted in conducting the study. The manuscript is well-written, highlighting the background of current study, limitations/challenges followed by scope of future actions towards promoting health in plateau environments. The work can be accepted for publication after addressing the following concerns:

Correction:

• Authors mentioned in the abstract that ‘fifty seven-week-old SPF-grade C57BL/6J male mice’ were used for the study but materials and methods section says fifty eight week. Please check and correct this.

• What do NPY and PYY correspond to in the ‘Measurement of appetite hormone content’ section? Explain the significance of these measuring these two contents for better understanding of the readers.

• Which ‘spectrophotometer’ was used to measure the purity and concentration of extracted DNA? Provide the details.

• Provide the reference for ‘four parameter logistic function’.

• Several sentences need to be rephrased for clarity like;

‘Overcoming the adverse effects………………………………………………….…solved urgently.’

‘Furthermore, the mechnanism……………………………………………………inulin was analyzed.’

‘Were/was’ used at several places in the results and discussion section.

‘pH’ written as ‘PH’.

‘Inulin’ should be written in lower case whenever it appears in the middle of the sentence.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: No

Reviewer #3: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Attachments

Attachment

Submitted filename: Report.pdf

Inulin promotes appetite in mice by regulating the gut microbiota under conditions of rapid entry to the plateau

PONE-D-24-29210R2

Dear Dr. Li,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Yash Gupta, Ph.D.

Academic Editor

PLOS ONE

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