Therapeutic Potential of Human Microbiome-Based Short-Chain Fatty Acids and Bile Acids in Liver Disease

Round 1

Reviewer 1 Report

The review article entitled “Therapeutic Potential of Microbiome-Based Short-Chain Fatty Acids in Liver Disease” aims to provide a brief update on SCFAs and BAs in terms of their cellular and molecular processes of metabolism in the context of gastrointestinal and clinical manifestations. However, the review needs some thorough revision to be considered for publication.

 

Major comments:

 

1.     Most importantly, the review needs thorough editing by an English writing expert. There are numerous errors in sentence construction which make the text illegible. As such, often, the message that the authors are trying to deliver doesn’t stand out. Hence some parts of the review seem confusing making it very difficult to understand the point the authors are trying to make.

2.     The introductory paragraph sets the tone for the entire review. This paragraph, however, mentions bacterial heterogeneity in stem cell transplants, etc, a sentence which seems abrupt and inappropriate in the beginning. It could be included later but preferably not in the beginning as the whole review does not revolve around on specific area of pathological process. The introductory paragraph should be structured in a way to inform the readers about SCFAs and BAs and why they are important.

3.     The objective of the review is to provide updates on both SCFAs and Bas, but the authors have only discussed SCFAs in detail, why?

4.     The heading, ‘SCFAs modulation and cellular setting’ should be changed to ‘Modulatory role of SCFAs’ or something similar as this paragraph discusses modulatory effects of SCFA on signaling mechanisms. 

5.     Since this is an update, the authors must include a table highlighting all studies in the past 5-10 years where SFCAs or BAs have been implicated in pathological processes especially gastrointestinal disorders.

6.     In my opinion, addition of a separate section highlighting the studies where SFCAs or BAs were actually explored as therapeutic modalities and their outcomes would greatly enhance the merit of the review.

7.     The review lacks a proper concluding paragraph highlighting the gaps/limitations in the field and the significance of this field of research and its future scope.

 

Minor comments

1.     Line 80-81, please cite the article at first mention as well.

2.     Line 81-81, …..’evolution in intentional epithelium’, What is this? The authors need to take care of many such typographical errors.

3.     Please re-write Lines 67-71.

4.     Please re-write Lines 90-94. The message is not clear.

 

 

Author Response

Comments and Suggestions for Authors

 

The review article entitled “Therapeutic Potential of Microbiome-Based Short-Chain Fatty Acids in Liver Disease” aims to provide a brief update on SCFAs and BAs in terms of their cellular and molecular processes of metabolism in the context of gastrointestinal and clinical manifestations. However, the review needs some thorough revision to be considered for publication.

 

Response: We are grateful for the reviewer’s valuable comments. Much thanks for your scientific commentaries and appreciation of our opinion manuscript. As per your concerns, we added the following details in manuscript and revised whole manuscript as reviewer pointed.
According to Livers guidelines, there is words limit for opinion manuscript. Also, this manuscript is covered in small section of short- chain fatty acids (SCFAs) and bile acids (BAs). Our chosen topics are novel for clinical and translation medicine. We feel, this opinion manuscript is mandatory in liver scientific community.

 

Major comments:

 

 

1. Most importantly, the review needs thorough editing by an English writing expert. There are numerous errors in sentence construction which make the text illegible. As such, often, the message that the authors are trying to deliver doesn’t stand out. Hence some parts of the review seem confusing making it very difficult to understand the point the authors are trying to make.

 

Response: We done official language edition before summation to the journal. Thanks for your comments.

 

2. The introductory paragraph sets the tone for the entire review. This paragraph, however, mentions bacterial heterogeneity in stem cell transplants, etc, a sentence which seems abrupt and inappropriate in the beginning. It could be included later but preferably not in the beginning as the whole review does not revolve around on specific area of pathological process. The introductory paragraph should be structured in a way to inform the readers about SCFAs and BAs and why they are important.

Response: we revised the SCFAs and BAs importance in revised manuscript.

 

 

3. The objective of the review is to provide updates on both SCFAs and Bas, but the authors have only discussed SCFAs in detail, why?

 

Response: We agree to the reviewer’s comment. BAs is now more discussed in the revised manuscript.

 

4. The heading, ‘SCFAs modulation and cellular setting’ should be changed to ‘Modulatory role of SCFAs’ or something similar as this paragraph discusses modulatory effects of SCFA on signaling mechanisms.

 

Response: We agree to your comment. We edited the section heading as “Modulatory role of SCFAs”.  

 

5. Since this is an update, the authors must include a table highlighting all studies in the past 5-10 years where SFCAs or BAs have been implicated in pathological processes especially gastrointestinal disorders.

 

Response: We apologize for missing the tables. This is opinion article so We have now revised the Table 1 in manuscript.

 

6. In my opinion, addition of a separate section highlighting the studies where SFCAs or BAs were actually explored as therapeutic modalities and their outcomes would greatly enhance the merit of the review.

 

Response: As per reviewer points, we have now modified it according to your instructions.

 

7. The review lacks a proper concluding paragraph highlighting the gaps/limitations in the field and the significance of this field of research and its future scope.

 

Response:  We agree to your comment. We added the short conclusion part. 

 

Minor comments

 

1. Line 80-81, please cite the article at first mention as well.

 

Response: we have corrected the sentence.

 

2. Line 81-81, …..’evolution in intentional epithelium’, What is this? The authors need to take care of many such typographical errors.

 

Response: we have corrected the sentence.

 

3. Please re-write Lines 67-71.

 

Response: We have completely revised it according to your instructions.

 

4. Please re-write Lines 90-94. The message is not clear.

 

Response: We have completely revised the sentence in manuscript. Thanks.

Author Response File: Author Response.docx

Reviewer 2 Report

In this manuscript, Ganesan. et.al reviewed the therapeutic potential of microbiome-based short-chain fatty acids (SCFAs) in liver disease. This review highlighted the significance of SCFAs and BA derivatives from microbiota and tried to link their existence with the progress of inflammation and carcinogenesis, and then liver diseases. As a review, it has obvious drawbacks in writing:

1. The authors discussed the therapeutic potential of both short-chain fatty acids and bile acids derived from the microbiome in the full text. However, they only pinpointed the short-chain fatty acids in the title. I cannot see the preference for focusing on the SCFAs. So I suggested authors add BAs in the title.
2. The authors aimed to link the microbiome-derived compounds to liver disease. However, there is a scarce illustration of how these compounds influence liver disease. They showed too much ‘indirect’ evidence, such as inflammation. But how liver disease, such as NASH, is induced by dysregulation is unclear. In result 4, the authors had very a summary of liver disorders. This part is an essential one. A figure or chart should be presented here. The authors must add more info to clarify this connection.
3. The whole manuscript lacks molecular mechanism demonstration:

(1) The function of histone deacetylase (HDAC) is an interesting point in this review. The authors even made it a major conclusion, as it is demonstrated in the Abstract. However, I cannot find any evidence of how HDAC regulates this process. What genes are regulated by HDAC concerning their acetylation level? Are these changes essential for the pathogenesis of liver diseases? The authors must have a more detailed summary.

(2) The similar problem also applies to the SCFA functions in immunological reactions.

(3) The same problem is for “Acetate could inhibit hormone sensitive lipase (HSL) phosphorylation in human multipotent adipose tissue derived stem adipocytes in a G-coupled manner”.

1. There is no conclusion and perspective in the review.
2. There are too few references.
3. In figure1, there are many details shown in figure1 but not discussed in the article, which is not acceptable.
4. Pay attention to the figure quality: the arrow in Figure1 is not straight.

 

Author Response

# Reviewer 2:

 

Comments and Suggestions for Authors

In this manuscript, Ganesan. et.al reviewed the therapeutic potential of microbiome-based short-chain fatty acids (SCFAs) in liver disease. This review highlighted the significance of SCFAs and BA derivatives from microbiota and tried to link their existence with the progress of inflammation and carcinogenesis, and then liver diseases.

 

Response: Much thanks for these wonderful scientific points of revisions and positive appreciation of our opinion manuscript. As per your scientific comments, we are revised the manuscript that prepared without damaging the structure, shape, and quality of science in this opinion manuscript.  

 

As a review, it has obvious drawbacks in writing:

1. The authors discussed the therapeutic potential of both short-chain fatty acids and bile acids derived from the microbiome in the full text. However, they only pinpointed the short-chain fatty acids in the title. I cannot see the preference for focusing on the SCFAs. So I suggested authors add BAs in the title.

 

Response: We agree with the reviewer’s comment. It is now corrected in the revised manuscript. New title: Therapeutic Potential of Human Microbiome-Based Short-Chain Fatty Acids and Bile acids in Liver Disease

 

1. The authors aimed to link the microbiome-derived compounds to liver disease. However, there is a scarce illustration of how these compounds influence liver disease. They showed too much ‘indirect’ evidence, such as inflammation. But how liver disease, such as NASH, is induced by dysregulation is unclear. In result 4, the authors had very a summary of liver disorders. This part is an essential one. A figure or chart should be presented here. The authors must add more info to clarify this connection.

 

Response: we have corrected the figure and placed in respective place. Discussed about NASH in direct evidence as shortly. 

 

1. The whole manuscript lacks molecular mechanism demonstration:

• The function of histone deacetylase (HDAC) is an interesting point in this review. The authors even made it a major conclusion, as it is demonstrated in the Abstract. However, I cannot find any evidence of how HDAC regulates this process. What genes are regulated by HDAC concerning their acetylation level? Are these changes essential for the pathogenesis of liver diseases? The authors must have a more detailed summary.

Response: HDAC responsible for transcriptional gene silencing. HDAC inhibiters in liver disease are key point to exploit specific therapeutic strategies.

 

• The similar problem also applies to the SCFA functions in immunological reactions.

Response: We agree with the reviewer’s comment. It is now corrected in the revised manuscript.

 

 

• The same problem is for “Acetate could inhibit hormone sensitive lipase (HSL) phosphorylation in human multipotent adipose tissue derived stem adipocytes in a G-coupled manner”.

Response:

 

1. There is no conclusion and perspective in the review.

Response: It is now corrected in the revised manuscript.

 

 

1. There are too few references.

Response:  It is now corrected in the revised manuscript. However, this is opinion article. So we cited limited reference. 

 

1. In figure1, there are many details shown in figure1 but not discussed in the article, which is not acceptable.

Response: It is now corrected in the revised manuscript.

 

1. Pay attention to the figure quality: the arrow in Figure1 is not straight.

Response: It is now corrected in the revised manuscript.

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The review article entitled “Therapeutic Potential of Microbiome-Based Short-Chain Fatty Acids in Liver Disease” aims to provide a brief update on SCFAs and BAs in the context of gastrointestinal and clinical manifestations. I appreciate that the authors have incorporated several of my comments raised earlier. The authors claim to have revised the article for English language but there are still several grammatical errors and errors in sentence structure.

 

I understand that it might be difficult for non-native English speakers to assess for errors in English language, but I would like to emphasize that correct English plays a very important role in communicating the message of the article. It also reflects the overall quality of the article and the efforts made by the authors in publishing their thoughts.

 

Major Comments:

1. As an example I am suggesting a few edits in the first paragraph of the introduction (Line 30-41)

1.     Line 30: Delete ‘The’ and begin the statement with “Trillions of…..”

2.     Line 30: change ‘were colonizing’ to ‘colonize’.

3.     Line 30: change ‘that collectedly’ to ‘that are collectively’.

4.     Line 31: change ‘mutuality’ to ‘mutually’.

5.     Line 32: delete the letter ‘a’ before ‘synergetic cellular metabolism’.

6.     Line 36: remove extra space after ‘BA)’

7.     Line 39: change ‘could altered’ to ‘could be altered’

8.     Line 39: change ‘process’ to ‘processes’

9.     Line 40: change ‘Intestinal microbiota shown that’ to ‘Analysis of intestinal microbiota shows that’.

 

These changes are necessary to make this paragraph clear for wide readership and also improve the quality of written text. There are innumerable instances in the entire article that needs extensive editing. So, I would strongly suggest the authors to get their article thoroughly checked and edited by a co-author with full professional proficiency in English to thoroughly revise the grammar of this manuscript. These services are also provided by some English proof-reading services for a fee.

 

2. Line 38: ‘smooth prompting host cyclic performance’. This phrase is not clear to me. I looked at reference 3, 4. Are the authors referring to cycles of equilibrium and imbalance at the commensal-host interface?

Author Response

Comments and Suggestions for Authors

 

The review article entitled “Therapeutic Potential of Microbiome-Based Short-Chain Fatty Acids in Liver Disease” aims to provide a brief update on SCFAs and BAs in the context of gastrointestinal and clinical manifestations. I appreciate that the authors have incorporated several of my comments raised earlier. The authors claim to have revised the article for English language but there are still several grammatical errors and errors in sentence structure.

 

I understand that it might be difficult for non-native English speakers to assess for errors in English language, but I would like to emphasize that correct English plays a very important role in communicating the message of the article. It also reflects the overall quality of the article and the efforts made by the authors in publishing their thoughts.

 

 Response: We are grateful for the reviewer’s valuable comments. We apologize for causing confusions. We corrected sentence and explained. However, we checked the grammatical errors in whole manuscript.

 

Major Comments:

1. As an example I am suggesting a few edits in the first paragraph of the introduction (Line 30-41)
2. Line 30: Delete ‘The’ and begin the statement with “Trillions of…..”

Response: It was corrected in the manuscript.

2. Line 30: change ‘were colonizing’ to ‘colonize’.

Response: It was corrected in the manuscript.

3. Line 30: change ‘that collectedly’ to ‘that are collectively’.

Response: It was corrected in the manuscript.

4. Line 31: change ‘mutuality’ to ‘mutually’.

Response: It was corrected in the manuscript.

5. Line 32: delete the letter ‘a’ before ‘synergetic cellular metabolism’.

Response: We erased sentence and explained.

6. Line 36: remove extra space after ‘BA)’

Response: It was corrected in the manuscript.

7. Line 39: change ‘could altered’ to ‘could be altered’

Response: It was corrected in the manuscript.

8. Line 39: change ‘process’ to ‘processes’

Response: It was corrected in the manuscript.

9. Line 40: change ‘Intestinal microbiota shown that’ to ‘Analysis of intestinal microbiota shows that’.

Response: It was corrected in the manuscript.

 

These changes are necessary to make this paragraph clear for wide readership and also improve the quality of written text. There are innumerable instances in the entire article that needs extensive editing. So, I would strongly suggest the authors to get their article thoroughly checked and edited by a co-author with full professional proficiency in English to thoroughly revise the grammar of this manuscript. These services are also provided by some English proof-reading services for a fee.

Response: As per your suggestion, we edited the full manuscript with professional editor. Now we have now improved the manuscript with more scientific sounds. Thanks.

 

2. Line 38: ‘smooth prompting host cyclic performance’. This phrase is not clear to me. I looked at reference 3, 4. Are the authors referring to cycles of equilibrium and imbalance at the commensal-host interface?

Response: We apologize for causing confusions. We erased sentence and explained.

We are revised the manuscript that prepared with scientific sounds in this opinion article.

 

Author Response File: Author Response.docx

Reviewer 2 Report

Thank authors to address my concerns one by one. I think the quality of the manuscript is greatly improved of the revised version. I do not have more comments.

Author Response

Comments and Suggestions for Authors

 

Thank authors to address my concerns one by one. I think the quality of the manuscript is greatly improved of the revised version. I do not have more comments.

Answer to Reviewer-2: Much thanks for these wonderful scientific points of revisions and positive appreciation of our opinion manuscript. Thank you.

Author Response File: Author Response.docx