PONE-D-22-30672Seasonal variations in gut microbiota and disease course in patients with inflammatory bowel diseasePLOS ONE

Dear Dr. Takehara,

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Additional Editor Comments :

Please revise the manuscript as advised by the reviewers

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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

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: 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: In this study, Mizuki Tani, et al. investigated the seasonality of fecal microbiota composition of inflammatory bowel disease patients and conclude that oral commensals Actinomyces and its symbiont TM7-3 fluctuated in the feces of Crohn’s disease patients by season.

Strengths of this study:

Study question is valid.

Adequate literature review was performed.

Results are clearly described.

Suggestions to consider:

- Study is limited by small sample size and including mostly patients with stable clinical activity index during the study period. Factors contributing to seasonal changes in Actinomyces and TMT-3 in CD patients is not discussed clearly.

- Did authors study other confounding factors that may affect gut microbiome like smoking, alcohol use, obesity, etc?

- Did authors notice any differences in microbiome with age and sex?

Reviewer #2: This manuscript examined the fecal microbiota of patients with inflammatory bowel disease, revealing seasonal changes in the gut microbiota. IBD is an urgent health issue, so this manuscript is timely. Overall, the manuscript is well written and the conclusions are fully supported by the findings. However, more polish should be considered. In my opinion, suitable revision should be conducted by the authors to ensure this manuscript can meet the standard quality of the PLoS One.

1. This paper mainly studies the influence of seasonal changes on intestinal flora, temperature and the diet may be the important factors, etc. Although all experimental materials were obtained in the same hospital, but they cannot represent the comparability of patients' living environment and eating habits, so it is necessary to describe the relevant background in detail.

2. The comment HV represented by the blue circle in Figure1 B should be changed to HC.

3. The format of references is not uniform, for example, in the line 556“de Vries SAG”. So all the references should be carefully verified.

4. The pictures in the full text are not clear.

5. Latin words such as Actinobacteria, etc. should be italicize.

6. The abundance of phyla Actinobacteria and TM7 in autumn was compared with spring and winter, why the summer was not mentioned?

7. Line 161-162“The median (range) ages of CD and UC 162 patients and HCs were 44 (32-55), 47 (44-57), and 33 (32-43) years, respectively.”

The age of the test group and the control group are also quite different. Do you consider the influence of age on the regulating ability of the flora, that is, the younger people have better regulating ability, so they do not get sick? Why not choose a control group of the similar age?

8. Line 284, The annotation format of references is incorrect.

9. In the full text and in the chart, p values are not written in standard at many places: line 186, p<.005 is changed to p<0.005; Change p<.0001 to p<0.0001 in line 187; Change p<.0001 to p<0.0001 in line 191; Change p<.0083 to p<0.0083 in line 220; Change p<.0083 to p<0.0083 at 228; In Fig5, change p<.0001 to p<0.0001 on the right side of figure CD; In S5A, p<.0001 is changed to p<0.0001

10. Supplementary chart missing: The chart mentioned in 250 lines of S5C Fig is missing.

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Reviewer #1: No

Reviewer #2: No

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Submitted filename: recomment.docx

Seasonal variations in gut microbiota and disease course in patients with inflammatory bowel disease

PONE-D-22-30672R1

Dear Dr. Takehara,

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.

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Kind regards,

Farah Al-Marzooq, MD, PhD

Academic Editor

PLOS ONE