PONE-D-24-03902Evaluation of the fatty acid-based erythrocyte membrane lipidome in cats with Food Responsive Enteropathy, Inflammatory Bowel Disease and Low-Grade Intestinal T-Cell LymphomaPLOS ONE

Dear Dr. Crisi,

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Juan J Loor

Academic Editor

PLOS ONE

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2. We noted in your submission details that a portion of your manuscript may have been presented or published elsewhere. [A related paper, intended to assess the impact of age, body weight, sex, and lifestyle on the fatty acid-based erythrocyte membrane lipidome of healthy cats, is currently under review by the journal Veterinary Medicine International. The cohort of healthy cats examined in this related paper is the same being considered in the herein submitted manuscript] Please clarify whether this [conference proceeding or publication] was peer-reviewed and formally published. If this work was previously peer-reviewed and published, in the cover letter please provide the reason that this work does not constitute dual publication and should be included in the current manuscript.

3. We notice that your supplementary [S1 and S2 Fig.] are included in the manuscript file. Please remove them and upload them with the file type 'Supporting Information'. Please ensure that each Supporting Information file has a legend listed in the manuscript after the references list.

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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: No

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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: No

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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: I would like to express my gratitude to the authors for sharing their fascinating study. The paper delves into the fatty acid profiles of the RBC membrane in both healthy cats and those with chronic enteropathies, with a thorough and well-articulated description of the study populations and methods. The introduction and discussion are highly informative, providing valuable insights into the topic. However, the results may benefit from some refinement, and the references require meticulous editing. Any typographical or grammatical errors should be corrected.

General comments:

• Please reconcile CE or FCE throughout the manuscript

• Please reconcile PUFA w-3 or w-3 PUFA

Detailed comments:

Line 1: Title: mixed case or sentence case?

Abstract

The word count of the abstract exceeds the limit. Please carefully read the author's guidelines.

Line 30, Gas chromatography “with which detection device (UV, MS, or others)” was used to quantitatively analyze a cluster of 11 “FAs”,

Line 31, “Including lipid homeostasis and enzyme activity indexes” This part is confusing. Those are not directly measured by the GC, but a calculation based on the results. Make it clear.

Line 34, “PUFA” should not be abbreviated without the full name if only appears once.

Line 37, “subgroups” of CE. No paragraphs in the abstract.

Line 38, In “humans” and dogs

Introduction

Line 80: UC and CD first appear.

Line 84: Check the abbreviation and provide their full names if first appear.

Materials and methods

Line 107: be specific, which serum biochemistry profile

Line 108: feline “serum” pancreatic lipase “i…”

Lines 128-132: need more polish.

Line 142: FAME?

Lines 145-149: please explain the information in the parentheses.

Line 150: explains which are SFA, MUFA, PUFA, w-6 and w-3. A table summarizing the information would be appreciated.

Line 162-163: Did you test the normality of your data? Which tests? Did you correct the p-values for multiple comparisons?

Results

Line 171: Basic information is lacking. Signalment for both groups. Move the S1 and S2 tables to the main text.

Line 174: Be specific “positively” what does it mean? Decreased of FCEAI? No clinical signs?

Line 191: PCA and heatmap might be good ways to visualize this dataset with multiple variables. Please add them for readers to better appreciate the changes.

Line 197: Are these P values corrected for multiple comparisons? Please add adjusted P-values or Q-values. What are the units of these variables? “IQR” is a better abbreviation for interquartile range.

Lines 201-207: Please add and make it clear that the FAs are from “RBC membranes” in the context and captions of tables and figures. For example, concentrations of DPA in RBC membranes. FAs can be measured in other biological matrixes as well. Some representative figures would help readers to appreciate the differences between groups. The quality of the supplementary figures is poor. I am not sure if it’s due to the end of the submission portal or from the authors.

Line 206: Table 3 can be in the supplementary data or have some representative figures of some results.

Line 217: Hypocobalaminemic cats (n=?), the changes were compared to which population?

Line 220: No difference of what?

Lines 222-225: Please add the 95% confidence interval and the numbers of observations of each statistic. For example, xyz acid (r = 0.25, 95% CI [0.18-0.33], n = 65, p = 0.002)

Discussion

While this journal does not impose any word limit, it is recommended to consider editing/removing certain portions of both mice and human studies. This would ensure that the content is concise and impactful, leading to better engagement and understanding among readers in veterinary medicine.

Line 238: Kindly explain how metabolic differences between the two species.

Line 243: Do you know if certain fatty acids are essential to add to cat’s diet according to NRC, AFFCO, or other authorities? What are the most common fatty acids found in their diet? Any differences between extruded diet and canned food?

Line 245: cats “with CE”. Please reconcile throughout the whole manuscript.

Line 250-251: missing reference.

Line 253: be specific, how long is the lifespan.

Line 255: be specific, how consistent, and stable? Over how long of the duration?

Line 264: cats with “CE”

Line 265: why only mention IBD? In humans or cats?

Line 269: missing reference.

Line 275: FAs concentrations in serum? Feces? Or RBC membranes? Not clear. How large is the study sample size?

Line 289: be specific. “notable” what does it mean? How many fold differences? No overlapping between groups or statistically different? Same analytical method from your study and this study?

Line 291: Check the author’s name.

Line 313: Check the references.

Line 336: Check the references.

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Reviewer #1: No

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Evaluation of the fatty acid-based erythrocyte membrane lipidome in cats with food responsive enteropathy, inflammatory bowel disease and low-Grade Intestinal T-cell lymphoma

PONE-D-24-03902R1

Dear Dr. Crisi,

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,

Juan J Loor

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #1: All comments have been addressed

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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 #1: Yes

**********

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

Reviewer #1: Yes

**********

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 #1: 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 #1: Yes

**********

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 #1: I would like to thank the authors for their hard work on revising the papers. They addressed all the questions, and the current revision is suitable for publication.

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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 #1: Yes: Chi-Hsuan Sung

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