Gut Dysbiosis, Malnutrition and Sarcopenia in Liver Cirrhosis: A Narrative Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Well conducted narrative review about comorbidities associated with liver cirrhosis.

The review is fluent, enjoyable and provides a brief review on the topic.

I believe the paper is ready for publication; I would suggest to create a visual abstract to make it even more attractive.

Evaluation according to the SANRA guidelines:

1) Justification of the article importance: Adequate.   

2) Statement of concrete aim: Adequate

3) Description of the literature search: Adequate

4) Referencing: Adequate

5) Scientific reasoning: Adequate

6) Presentation of data: Adequate; may be improved with visual abstract

Author Response

Dear Editor and Reviewers,

We would like to sincerely thank you for your careful evaluation of our manuscript and for the constructive comments, which have significantly improved the clarity and scientific depth of our work. We have carefully revised the manuscript in accordance with all suggestions. All changes have been highlighted in yellow in the revised version of the manuscript.

Below, we provide a detailed response to the reviewers’ comments.

To The Editor:

 We sincerely thank the Editor for the constructive suggestions. In accordance with the recommendation, we have extended the main text (from the Introduction to the Conclusions section) to exceed 4000 words. We believe that this expansion has improved the depth, clarity and comprehensiveness of the manuscript.

 

Reviewer 1 Comments : Well conducted narrative review about comorbidities associated with liver cirrhosis.

The review is fluent, enjoyable and provides a brief review on the topic.

I believe the paper is ready for publication; I would suggest to create a visual abstract to make it even more attractive.

Evaluation according to the SANRA guidelines:

1) Justification of the article importance: Adequate.   

2) Statement of concrete aim: Adequate

3) Description of the literature search: Adequate

4) Referencing: Adequate

 

Response to Reviewer 1:

Thank you for your valuable suggestion. We have now created a visual abstract to enhance the presentation and overall attractiveness of the manuscript.

 Thank you for your consideration.

Reviewer 2 Report

Comments and Suggestions for Authors

Authors reviewed that gut dysbiosis, malnutrition and sarcopenia in liver cirrhosis. This looks important in this area.

1. In abstract section, authors mentioned “Furthermore, gut dysbiosis, a key feature of advanced liver disease, contributes to impaired digestion, malabsorption of macro- and micronutrients, increased intestinal permeability, malnutrition and systemic inflammation. These alterations promote negative energy balance, reduce muscle protein synthesis and enhance muscle catabolism, thereby accelerating muscle wasting.” Authors should add these illustration in the text.
2. In “4.5. Knowledge gaps and future directions” section, authors should add the therapies, such as rehabilitation. See the reference: Terai S, et al. Guidance for Liver Rehabilitation in Chronic Liver Disease. Hepatol Res. 2026 Jan 31. doi: 10.1111/hepr.70132. Online ahead of print. PMID: 41618983

Author Response

Reviewer 2 Comments:

Authors reviewed that gut dysbiosis, malnutrition and sarcopenia in liver cirrhosis. This looks important in this area.

1. In abstract section, authors mentioned “Furthermore, gut dysbiosis, a key feature of advanced liver disease, contributes to impaired digestion, malabsorption of macro- and micronutrients, increased intestinal permeability, malnutrition and systemic inflammation. These alterations promote negative energy balance, reduce muscle protein synthesis and enhance muscle catabolism, thereby accelerating muscle wasting.” Authors should add these illustration in the text.
2. In “4.5. Knowledge gaps and future directions” section, authors should add the therapies, such as rehabilitation. See the reference: Terai S, et al. Guidance for Liver Rehabilitation in Chronic Liver Disease. Hepatol Res. 2026 Jan 31. doi: 10.1111/hepr.70132. Online ahead of print. PMID: 4161898 

Response to Reviewer 2:

We appreciate this valuable suggestion. In response, we have expanded section 4.6 (Knowledge gaps and future directions) to include a discussion on structured liver rehabilitation programs as an emerging therapeutic strategy in chronic liver disease. Specifically, we added a new paragraph describing the role of individualized exercise-based liver rehabilitation integrated with nutritional support and multidisciplinary care. We also incorporated the recommended reference (Terai et al., 2026) to support the clinical relevance of rehabilitation in preventing frailty progression and improving outcomes in advanced liver disease. This addition strengthens the translational and therapeutic perspective of our review and better aligns the manuscript with current evidence-based management strategies.

Thank you for your consideration.

Reviewer 3 Report

Comments and Suggestions for Authors

It is a review summarizing current knowledge on gut-liver-muscle axis looking at sarcopenia. Subject is vibrant as most of studies are published recent years. My main concern is lack of critical view on available data.

Liver cirrhosis was selected as representant of  chronic liver disease. It is well known that cirrhosis covers large clinical spectrum ranging from early compensated to end-stage decompensated liver disease (in elastography liver stiffness may range from 20 kPa to 70kPa). It is also well evidenced that patients with late cirrhosis suffer from sarcopenia and patients with all stages of cirrhosis demonstrate SIBO and/or gut dysbiosis proportional to liver failure, but much less is known on direct relationships between dysbiosis and sarcopenia. In literature I did not find no one paper specifically investigating this issue. In effect, among tables shown in manuscript this relationship was not in center of interest.

In addition, most cause-effect relationships between dysbiosis and liver function or liver function and sarcopenia are based on hypotheses and sometimes speculations, as they were investigated separately.  It is not unexpected, as decompensated cirrhosis provides background for whole spectrum of pathologies creating multidirectional associations. Good example is hyperammonemia resulting from dysbiosis, liver failure and portal hypertension (collateral circulation), which on one side damages skeletal muscles, but on the other side loss of muscle mass diminishes capability of ammonia metabolism. It would be more reasonable to show results coming from different studies according to stages of cirrhosis (compensated vs decompensated).

It should also be checked if some relevant studies were not overlooked in search strategy including only “gut dysbiosis” and omitting in keywords such terms as “intestinal microbiota, SIBO..”). 

 

Author Response

Reviewer 3 Comments:

It is a review summarizing current knowledge on gut-liver-muscle axis looking at sarcopenia. Subject is vibrant as most of studies are published recent years. My main concern is lack of critical view on available data.

Liver cirrhosis was selected as representant of  chronic liver disease. It is well known that cirrhosis covers large clinical spectrum ranging from early compensated to end-stage decompensated liver disease (in elastography liver stiffness may range from 20 kPa to 70kPa). It is also well evidenced that patients with late cirrhosis suffer from sarcopenia and patients with all stages of cirrhosis demonstrate SIBO and/or gut dysbiosis proportional to liver failure, but much less is known on direct relationships between dysbiosis and sarcopenia. In literature I did not find no one paper specifically investigating this issue. In effect, among tables shown in manuscript this relationship was not in center of interest.

In addition, most cause-effect relationships between dysbiosis and liver function or liver function and sarcopenia are based on hypotheses and sometimes speculations, as they were investigated separately.  It is not unexpected, as decompensated cirrhosis provides background for whole spectrum of pathologies creating multidirectional associations. Good example is hyperammonemia resulting from dysbiosis, liver failure and portal hypertension (collateral circulation), which on one side damages skeletal muscles, but on the other side loss of muscle mass diminishes capability of ammonia metabolism. It would be more reasonable to show results coming from different studies according to stages of cirrhosis (compensated vs decompensated).

It should also be checked if some relevant studies were not overlooked in search strategy including only “gut dysbiosis” and omitting in keywords such terms as “intestinal microbiota, SIBO..”). 

Response to Reviewer 3:

In response to the reviewers’ comments, we have revised the manuscript accordingly. In particular, we expanded section 4.5 (Critical appraisal of current evidence) to provide a more rigorous evaluation of current limitations, including the predominantly indirect nature of the evidence linking gut dysbiosis and sarcopenia, the heterogeneity of cirrhosis stages, and the lack of prospective studies specifically designed to assess the gut–liver–muscle axis. We also emphasized the need for integrated longitudinal studies combining microbiome profiling and objective muscle assessment. All modifications have been highlighted in the revised manuscript.

 We believe that these revisions have improved the completeness and clinical applicability of our manuscript. We are grateful for the reviewers’ insightful comments and hope that the revised version meets the expectations of the journal.

Thank you for your consideration.

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

I accept replies and I believe that now general receipt of this review will be better i