Title: Relationship between gut microbiota dysbiosis and bile acid in patients with hepatitis B-
induced cirrhosis
Version: 2 Date: 20 Jun 2025
Reviewer:  Giuseppe Guido Maria Scarlata
Reviewer's report:
This study aimed to investigate the relationship between the gut microbiota and BAs in patients
with HBC. The identification of gut microbiota with high specificity was performed in BA-
high patients, which may contribute to the identification of novel biomarkers for assessing and
monitoring HBC progression and provide new insights into therapeutic strategies targeting gut
microbiota-mediated bile acid metabolism in HBC management.
I have some suggestions to improve the manuscript:
1. Background is very poor. I suggest to add some important points about the gut microbiota
composition in health and disease (see: doi:10.3390/nu15163569);
2. Role of bile acids: although BA are mentioned to have “antibacterial” effects, the presented
data suggest higher BA levels associate with worse liver function and more dysbiosis,  a
contradiction that is not addressed;
3. The repeated reporting of phylum/class/order/family/genus level differences in Tables 2 and
4 creates excessive duplication (e.g., reporting "Bacilli," "Lactobacillales," "Streptococcaceae"
and "Streptococcus" together without synthesis);
4. Several indices (Shannon, Simpson) show no difference, yet authors claim differences in “#-
diversity.” This oversimplifies ecological complexity;
5. Clarify statistical test used in #-diversity PCA (e.g., PERMANOVA?) and report its p-value
and R²;
6. Underline the strenghts and the limitations of your study.
Title: Relationship between gut microbiota dysbiosis and bile acid in patients with hepatitis B-
induced cirrhosis
Version: 2 Date: 20 Jun 2025
Reviewer:  Giuseppe Guido Maria Scarlata
Reviewer's report:
This study aimed to investigate the relationship between the gut microbiota and BAs in patients
with HBC. The identification of gut microbiota with high specificity was performed in BA-
high patients, which may contribute to the identification of novel biomarkers for assessing and
monitoring HBC progression and provide new insights into therapeutic strategies targeting gut
microbiota-mediated bile acid metabolism in HBC management.
I have some suggestions to improve the manuscript:
1. Background is very poor. I suggest to add some important points about the gut microbiota
composition in health and disease (see: doi:10.3390/nu15163569);
2. Role of bile acids: although BA are mentioned to have “antibacterial” effects, the presented
data suggest higher BA levels associate with worse liver function and more dysbiosis,  a
contradiction that is not addressed;
3. The repeated reporting of phylum/class/order/family/genus level differences in Tables 2 and
4 creates excessive duplication (e.g., reporting "Bacilli," "Lactobacillales," "Streptococcaceae"
and "Streptococcus" together without synthesis);
4. Several indices (Shannon, Simpson) show no difference, yet authors claim differences in “#-
diversity.” This oversimplifies ecological complexity;
5. Clarify statistical test used in #-diversity PCA (e.g., PERMANOVA?) and report its p-value
and R²;
6. Underline the strenghts and the limitations of your study.
Please review this paper.
user
Title: Relationship between gut microbiota dysbiosis and bile acid in patients with hepatitis B-
induced cirrhosis
Version: 2 Date: 20 Jun 2025
Reviewer:  Giuseppe Guido Maria Scarlata
Reviewer's report:
This study aimed to investigate the relationship between the gut microbiota and BAs in patients
with HBC. The identification of gut microbiota with high specificity was performed in BA-
high patients, which may contribute to the identification of novel biomarkers for assessing and
monitoring HBC progression and provide new insights into therapeutic strategies targeting gut
microbiota-mediated bile acid metabolism in HBC management.
I have some suggestions to improve the manuscript:
1. Background is very poor. I suggest to add some important points about the gut microbiota
composition in health and disease (see: doi:10.3390/nu15163569);
2. Role of bile acids: although BA are mentioned to have “antibacterial” effects, the presented
data suggest higher BA levels associate with worse liver function and more dysbiosis,  a
contradiction that is not addressed;
3. The repeated reporting of phylum/class/order/family/genus level differences in Tables 2 and
4 creates excessive duplication (e.g., reporting "Bacilli," "Lactobacillales," "Streptococcaceae"
and "Streptococcus" together without synthesis);
4. Several indices (Shannon, Simpson) show no difference, yet authors claim differences in “#-
diversity.” This oversimplifies ecological complexity;
5. Clarify statistical test used in #-diversity PCA (e.g., PERMANOVA?) and report its p-value
and R²;
6. Underline the strenghts and the limitations of your study.
assistant