Gut Microbiota and Sex Hormones: Crosstalking Players in Cardiometabolic and Cardiovascular Disease

Round 1

Reviewer 1 Report

The manuscript under the title: „ Gut microbiota and sex hormones: crosstalking players in cardiometabolic and cardiovascular disease” represents a very interesting review article describing the connection between gut microbiota (GM) dysbiosis and increased risk of cardiometabolic (CM) disorders and cardiovascular (CV) diseases. The authors have presented the molecular pathways linking microbiota-derived signals to the local activation of the immune system as a driver of a systemic proinflammatory state and permissive condition for the onset and progression of CM and CV disease. Also, the cross-talk between sex hormone and  GM and its impacts on disease susceptibility was outlined, thus offering mechanistic insight into sexual dimorphism observed in CVD.

 

The whole manuscript is well written in all its parts and adequately referenced with up-to-date literature reports.

 

I have enjoyed reading the presented review article in all its parts.

 

The only suggestion that I may have is connected to the lack of accompanying illustration (s) that will, in my opinion, further enrich this well-written, exciting, and pretty informative review of the corresponding literature.

 

The acceptance of the manuscript is firmly suggested.

Author Response

Reviewer 1

The manuscript under the title: “Gut microbiota and sex hormones: crosstalking players in cardiometabolic and cardiovascular disease” represents a very interesting review article describing the connection between gut microbiota (GM) dysbiosis and increased risk of cardiometabolic (CM) disorders and cardiovascular (CV) diseases. The authors have presented the molecular pathways linking microbiota-derived signals to the local activation of the immune system as a driver of a systemic proinflammatory state and permissive condition for the onset and progression of CM and CV disease. Also, the cross-talk between sex hormone and GM and its impacts on disease susceptibility was outlined, thus offering mechanistic insight into sexual dimorphism observed in CVD.

The whole manuscript is well written in all its parts and adequately referenced with up-to-date literature reports.

I have enjoyed reading the presented review article in all its parts.

Replay. We have really appreciated the positive remarks of the reviewer and are grateful for her/his suggestion.

1 The only suggestion that I may have is connected to the lack of accompanying illustration (s) that will, in my opinion, further enrich this well-written, exciting, and pretty informative review of the corresponding literature.

Replay. According to the reviewer’s suggestion, in the revised version we have added 3 figures and a graphical abstract.

Reviewer 2 Report

In this review focused gut microbiota, food, sex hormones and immune system as cross talking, gender-related, variables able to conditioning the onset and progression of cardio vascular disease. The manuscript is well structured and well discussed. However, some points should be checked and corrected before its acceptance in this journal. 

Therefore, according to my comments, I recommended the publication of the paper after major revision.

·         The abstract is not clear. Please add the aim and objective of the MS.

·         The study's background should be clearly stated. Describe the introduction and review of the work (Please add more information).

·         Please draw some good figure for easily understanding of the concept of review.

·         In Conclusion, the authors should add the significance of this research and its potential practical application.

·         The MS English needs to be improved. The article's English must be carefully checked for grammatical errors.

Author Response

Reviewer 2

In this review focused gut microbiota, food, sex hormones and immune system as cross talking, gender-related, variables able to conditioning the onset and progression of cardio vascular disease. The manuscript is well structured and well discussed. However, some points should be checked and corrected before its acceptance in this journal.

Replay. We have really appreciated the positive remarks of the reviewer and are grateful for her/his comments and suggestions.

1 The abstract is not clear. Please add the aim and objective of the MS.

Replay. According to the reviewer’s suggestion the objectives of the review have been made more explicit either in the abstract and in the introduction section as follows, line 11 “one major objective of this narrative review is to…” and lines 60-63 “The main objective is to provide an updated overview of the interconnected molecular mechanisms that may be effectively targeted by safe and low cost interventions aimed at reshaping GM and preserve the homeostasis of the endocrine and immune systems with the final goal to reduce the risk for CM and CVD”.

2 The study's background should be clearly stated. Describe the introduction and review of the work (Please add more information).

Replay. We respectfully point out that this manuscript is not a study, intended as an original article, but a narrative review. In the introduction section we have introduced GM, diet, SH and inflammation as major cross-talking players involved in the evolution of CM and CV disease. These introductive notions are intended as the background for a more detailed description reported in the dedicated paragraphs that follow. According to the reviewer’s suggestion, more information on the objectives and mail goal of the manuscript has been reported at the end of the introduction section, as described in the replay to point 1.

3 Please draw some good figure for easily understanding of the concept of review.

Replay. According to the reviewer’s suggestion, in the revised version we have added 3 figures and a graphical abstract.

4 In Conclusion, the authors should add the significance of this research and its potential practical application.

Replay. According to the reviewer’s suggestion the information has been added in lines 679-689 as follows “Despite its relatively early introduction in 2013 the concept of microgenderome, intended as the interaction between GM, SH, and immunity (170), has not been exhaustively framed in the context of CM and CV disease, especially in the clinical arena. Though preclinical researches have clearly demonstrated the involvement of microbiome-dependent bile acid metabolism, toll-like receptor signaling cascades, steroid hormone modulation, and immune responce as important drivers in sex differences in CVD risk, human studies are still lacking. The literature reviewed herein, while unveiling novel molecular pathways mainly emerged from animal models, highlights the critical importance of innovative human researches specifically designed to assess the role of GM, SH and inflammation as cross-talking players in the onset and progression of CM and CV disease.…”

5 The MS English needs to be improved. The article's English must be carefully checked for grammatical errors.

Replay..According to the reviewer’s suggestion the manuscript has been corrected by a native English speaker.

Round 2

Reviewer 2 Report

Requested corrections were completed.