Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is certainly a well-designed study, which showed in a mouse model how aerobic exercise can ameliorate age-related gut microbiota deterioration, characterized by overgrowth of pathogenic bacteria, by restoring gut microbiota homeostasis and reducing intestinal permeability. In particular, the authors demonstrated how exercise led to a significant increase in Akkermansia bacteria in feces, suggesting that this mucin-degrading bacterium is particularly responsive to exercise. Metabolomic profiling identified eicosanoid metabolism as the most significantly altered pathway, which can be regulated by continuous exercise. Multi-omics integration confirmed that exercise is a potent modulator of the gut-microbiota-metabolite axis during aging. Certainly, the results of the study provided insights into how exercise promotes healthy aging, identifying new targets for anti-aging strategies via the microbiota. However, the authors could provide further comments or suggestions in the conclusions, for example, on how these results could be transferred to clinical practice.

Author Response

Point-by-point response to Reviewer’s comments:

Reviewer #1 This is certainly a well-designed study, which showed in a mouse model how aerobic exercise can ameliorate age-related gut microbiota deterioration, characterized by overgrowth of pathogenic bacteria, by restoring gut microbiota homeostasis and reducing intestinal permeability. In particular, the authors demonstrated how exercise led to a significant increase in Akkermansia bacteria in feces, suggesting that this mucin-degrading bacterium is particularly responsive to exercise. Metabolomic profiling identified eicosanoid metabolism as the most significantly altered pathway, which can be regulated by continuous exercise. Multi-omics integration confirmed that exercise is a potent modulator of the gut-microbiota-metabolite axis during aging. Certainly, the results of the study provided insights into how exercise promotes healthy aging, identifying new targets for anti-aging strategies via the microbiota. However, the authors could provide further comments or suggestions in the conclusions, for example, on how these results could be transferred to clinical practice.

Response: We greatly appreciate this suggestion. As the reviewer recommended, we have accordingly incorporated future research prospects for clinical application in the “Conclusions” section of our revised manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

The title is informative but a bit long. Consider splitting it into two sentences or shortening to highlight the main finding directly.
Introduction сomment: Excellent background on aging and gut microbiota. However, consider shortening some sentences to improve readability and avoid overly long, complex phrases.
Comment: Specify whether multiple comparison corrections (e.g., Bonferroni) were applied to reduce type I errors.
Comment: The figures are clear and comprehensive. Ensure that all figure legends provide enough detail for interpretation without referencing the main text.

Author Response

Reveiwer #2: The title is informative but a bit long. Consider splitting it into two sentences or shortening to highlight the main finding directly.

Introduction сomment: Excellent background on aging and gut microbiota. However, consider shortening some sentences to improve readability and avoid overly long, complex phrases.

Comment: Specify whether multiple comparison corrections (e.g., Bonferroni) were applied to reduce type I errors.

Comment: The figures are clear and comprehensive. Ensure that all figure legends provide enough detail for interpretation without referencing the main text.

Response: We greatly appreciate this suggestion. As the reviewer recommended, we have implemented the following revisions:

1.Title Revision: We have refined the title for greater conciseness. The revised version reads: "Exercise Remodels Akkermansia-Associated Eicosanoid Metabolism to Alleviate Intestinal Senescence: Multi-Omics Insights ".

2. Introduction Enhancement: We have revised the “Introduction” section, transforming complex sentences into more concise, reader-friendly formulations while maintaining scientific rigor.
3. Statistical Methods: We have supplemented the description of the statistical methodologies used.
4. Figure Legends: We have meticulously reviewed all figure legends to ensure they provide sufficient detail for interpretation.