The causal relationship between gut microbiota and immune skin diseases: A bidirectional Mendelian randomization

Fei Feng; Ruicheng Li; Rui Tian; Xueyi Wu; Nannan Zhang; Zhenhua Nie

doi:10.1371/journal.pone.0298443

Peer Review History

Original SubmissionAugust 10, 2023
8 Dec 2023 Decision Letter - Donatella Mentino, Editor PONE-D-23-25279The causal relationship between gut microbiota and immune skin diseases: a bidirectional Mendelian randomizationPLOS ONE Dear Dr. feng, 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. Please submit your revised manuscript by Jan 21 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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Please amend the manuscript submission data (via Edit Submission) to include author Xueyi Wu and Nannan Zhang. Additional Editor Comments : In your work why have you only dealt with some skin pathologies? explain the discussion and conclusion better [Note: HTML markup is below. Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? 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Reviewer #1: Yes ****** 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: This is a bidirectional two-sample mendelian randomisation study that appraised the causal relationship between gut microbiota and skin diseases.The manuscript was well written, and analyses were comprehensively conducted. Nevertheless, the quality of this manuscript may be improved by addressing the following issues. Major: 1. The authors extracted GWAS summary statistics for skin diseases from the FinnGen study (data freeze 5) which was released in 2021 in 218,792 individuals. However, the most up-to-date datasets were released in April 2023, with much larger sample sizes (377,277 individuals). I would like to see the results using the most updated datasets. 2. I suggest calculating the statistical power for each MR analysis. 3. The formula to calculate F statistics seems wrong and the citation of references is confusing in section 2.1 line 111-114, please carefully check and revise these. Minor: 1. The colomns "mr_keep.exposure","pval_origin.exposure" and "id.exposure" are not necessary in supplementary table 1, please remove them. Since the "eaf.exposure" is not available for each SNP, please also remove it. 2. The colomns "id.exposure" and "id.outcome" are not necessary in supplementary tables 2-4, please remove it. 3. Please add P values for heterogeneity and pleiotropy from the IVW and MR Egger methods to supplementary tables 2-4. 4. The authors used different terms including "gut microbiota", "gut flora", and "intestinal flora" in differnet places, please use "gut microbiota" throughout the whole manuscript. ****** 6. 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Revision 1
28 Dec 2023 Author Response Dear Professor Donatella Mentino, We express our gratitude to you and the expert reviewers for the thorough examination and approval of our manuscript titled "The causal relationship between gut microbiota and immune skin diseases: a bidirectional Mendelian randomization" by Fei Feng et al. In this study, we utilized Mendelian randomization to explore the relationship between gut microbiota and several skin diseases. The results revealed a causal relationship between various microbial groups in the gut and conditions such as psoriasis, atopic dermatitis, acne, and lichen planus. Changes in the abundance of these microbial groups may contribute to the onset and progression of these skin disorders. Our findings underscore the significance of the gut-skin axis in clinical contexts and provide new insights into the treatment of skin diseases. We have carefully addressed the reviewers' suggestions, offering a point-to-point response to their comments. Enclosed, please find the revised manuscript with changes highlighted, along with a "clean" copy formatted according to the journal's requirements. We believe that these revisions, guided by the reviewers' critiques and Manuscript Edits, have substantially enhanced the quality of the manuscript, and we hope it meets the standards for publication in PLOS ONE. We appreciate your consideration in allowing us to revise our manuscript and eagerly anticipate your feedback. Sincerely, Fei Feng We thank the editor and the reviewers for their thorough examination of our manuscript, and the valuable and insightful comments provided. We have revised the manuscript accordingly and provided a point-to-point response to reviewers’ comments below. Editor Comments: In your work why have you only dealt with some skin pathologies? Author Response: In the manuscript, we focused on a subset of skin diseases, acknowledging a limitation in our coverage. Due to constraints related to time, resources, and the research direction of our team, we primarily addressed several common skin conditions encountered in our clinical work. This approach facilitates a more in-depth understanding and treatment approach to these diseases. Additionally, we recognize the potential for further clinical studies to validate the obtained results. Reviewers' comments: Reviewer #1： Major: 1. The authors extracted GWAS summary statistics for skin diseases from the FinnGen study (data freeze 5) which was released in 2021 in 218,792 individuals. However, the most up-to-date datasets were released in April 2023, with much larger sample sizes (377,277 individuals). I would like to see the results using the most updated datasets. Author Response: Thank you very much for your suggestions. We have realized that the data we initially used were from the FinnGen study (data freeze 5), which significantly differed in scale from the latest release. Consequently, we conducted a new Mendelian randomization (MR) analysis using the most recent data available as of December 18, 2023 (data freeze 10, 412,181 individuals). The results have been appropriately adjusted in the manuscript. With the increase in sample size, some findings from the initial analysis are no longer statistically significant in the second analysis. We believe that the results from the larger sample size are more reliable. We appreciate your guidance, which has contributed to the rigor and completeness of our study. 2. I suggest calculating the statistical power for each MR analysis. Author Response: Thank you very much for your advice. Indeed, we have considered the power for each Mendelian randomization (MR) analysis. However, the GWAS raw data for the gut microbiota we used lack the values for effect allele frequency (EAF) and minor allele frequency (MAF). Consequently, we were unable to calculate the power. We then supplemented the EAF values based on human "1000g" genomic data and computed the power accordingly. These results will be included in our supplementary files. While this approach enhances rigor, the authenticity and accuracy of the supplemented data may be subject to discussion. Therefore, we opted not to present these details in the main manuscript. 3. The formula to calculate F statistics seems wrong and the citation of references is confusing in section 2.1 line 111-114, please carefully check and revise these. 4. Author Response: I deeply apologize for errors made during the writing process. The citation issues for references 111-114 have been corrected. Regarding the calculation formula for F statistics, we explored various methods from relevant literature. The classic formula is F = R2(N-K-1)/K(1-R2), where R2 = 2β2 (1-MAF) MAF. However, due to the lack of EAF and MAF values in the original data, implementing this method proved challenging. Consequently, we opted for an alternative formula based on other literature, specifically F = β2 exposure/SE2 exposure. Minor: 1. The columns "mr_keep.exposure","pval_origin.exposure" and "id.exposure" are not necessary in supplementary table 1, please remove them. Since the "eaf.exposure" is not available for each SNP, please also remove it. 2. The columns "id.exposure" and "id.outcome" are not necessary in supplementary tables 2-4, please remove it. 3. Please add P values for heterogeneity and pleiotropy from the IVW and MR Egger methods to supplementary tables 2-4. 4. The authors used different terms including "gut microbiota", "gut flora", and "intestinal flora" in different places, please use "gut microbiota" throughout the whole manuscript. Author Response: Thank you very much for your guidance on the shortcomings of the manuscript. We have addressed each of the points you highlighted in the new draft, and these suggestions have contributed to making the paper more rigorous and scientifically sound. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0298443.r002
25 Jan 2024 Decision Letter - Donatella Mentino, Editor The causal relationship between gut microbiota and immune skin diseases: a bidirectional Mendelian randomization PONE-D-23-25279R1 Dear Dr.fei feng 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Donatella Mentino Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0298443.r003
Formally Accepted
8 Mar 2024 Acceptance Letter - Donatella Mentino, Editor PONE-D-23-25279R1 PLOS ONE Dear Dr. Feng, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Donatella Mentino Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0298443.r004

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