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PONE-D-21-31676Differential colitis susceptibility of Th1- and Th2-biased mice- A Multi-Omics ApproachPLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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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

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Reviewer #1: Mukhopadhyay et al performed experiments and analyses aimed at addressing the potential mechanisms underlying the differential colitis susceptibility between C57BL/6 (type 1-prone) and BALB/c (type 2-prone) mice. They employed multi-omics approaches including comparative transcriptomics, metabonomics, and metagenomics analyses. They found that, in C57BL/6, the severity of DSS-induced colitis was mainly host factor-driven, including pro-inflammatory host genes and host metabolites. On the contrary, in BALB/c, the disease severity was more affected by the microbiota, such as gut microbial composition and microbial metabolites. These are very useful datasets which could be very helpful for other investigators in choosing mouse strains to study DSS-colitis or other disease models, as well as in considering the candidate pro-/anti-inflammatory host genes, host metabolites, microbial strains, or microbial metabolites reported in this manuscript as potential mechanisms.

I only have some minor comments:

1. Lines 210 to 213 - “The shortlisted genes from the transcriptomics data are mainly related to the inflammatory responses of the host. In C57BL/6, genes were primarily associated with pro-inflammation, whereas in BALB/c, genes were related to anti-inflammation.” Given that these conclusion are foundations of this manuscript, I would suggest the authors to use a heat map to show the shortlisted genes as a part of a main figure.

2. Tables S3, S4 and S5 were only mentioned in the Materials and Methods section which is a waste of good data. I would suggest the authors to cite these tables in their main text.

Reviewer #2: The manuscritps presents a thorough analysis of DSS induced colitis in Th1 and Th2 biased mice strains, C57BL/6 and BALB/c resectively. In order to find clinical differences between strains, they use first a high dose of DSS (1 week), followed by a lower dose (1 week). En the second week of treatment BALB/c mice recover, while C57BL/6 don´t. Surprisingly, this results are not shown, although they could go to a suplementary figure. No data on clinical scores, hystology or bowel weight/length is presented, making results weaker. A simple figure describing the findings in this particular model should be included.

Than the authors study cytokines (Pro-inflamatory and tolerogenic) at different stages. Results regarding cytokines are quite consisting with other papers. The multiomics approach, regarding bowel genes and metabolites compares to changes in gut microbiota are a unique and highly interesting contribution of the article. The data analysis are sound and rigorous statiscal test are performed. The English is quite clear and easy to read.

The results are well dicussed and enrich the article.

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Reviewer #1: No

Reviewer #2: No

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Differential colitis susceptibility of Th1- and Th2-biased mice- A Multi-Omics Approach

PONE-D-21-31676R1

Dear Dr. Aich,

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,

Lili Chen

Academic Editor

PLOS ONE