Ethanol-Producing Micro-Organisms of Human Gut: A Biological Phenomenon or a Disease?

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript provides a systematic review of ethanol-producing gut microbes and their implications in human health. The structure is logical, with clear explanations of microbial species, metabolic pathways, disease associations, and therapeutic strategies. However, the inclusion of recent studies (e.g., from the past two years) is limited, and some conclusions may need updating to reflect emerging evidence. The authors are advised to incorporate the latest research findings to enhance the paper’s relevance and accuracy.

1, The labeling and data presentation in figures and tables need ‌enhanced clarity‌ to ensure consistency and readability. Consider revising axis labels, legends, and annotations to improve interpretability.

2, The manuscript requires ‌thorough proofreading‌ for grammatical errors, typos, and stylistic inconsistencies. For example, line 92 contains an obvious error that needs correction.

‌3, Repetitive or redundant phrasing‌ weakens the text. Phrases such as “it is felt that” and “another study found that” should be revised for conciseness and directness.

‌4, The abstract is ‌excessively lengthy‌ and would benefit from streamlining. Focus on condensing key findings, methodology, and conclusions to meet journal guidelines and improve readability.

Author Response

This manuscript provides a systematic review of ethanol-producing gut microbes and their implications in human health. The structure is logical, with clear explanations of microbial species, metabolic pathways, disease associations, and therapeutic strategies. However, the inclusion of recent studies (e.g., from the past two years) is limited, and some conclusions may need updating to reflect emerging evidence. The authors are advised to incorporate the latest research findings to enhance the paper’s relevance and accuracy.

1, The labeling and data presentation in figures and tables need ‌enhanced clarity‌ to ensure consistency and readability. Consider revising axis labels, legends, and annotations to improve interpretability.

2, The manuscript requires ‌thorough proofreading‌ for grammatical errors, typos, and stylistic inconsistencies. For example, line 92 contains an obvious error that needs correction.

‌3, Repetitive or redundant phrasing‌ weakens the text. Phrases such as “it is felt that” and “another study found that” should be revised for conciseness and directness.

‌4, The abstract is ‌excessively lengthy‌ and would benefit from streamlining. Focus on condensing key findings, methodology, and conclusions to meet journal guidelines and improve readability.

 

Reply

We thank the reviewer for criticism and suggestions.

Concerning the update of recent studies, we doubled checked with the two most comprehensive studies published, namely Ref. 7 and Ref. 10, both published in 2024 and found no paper we could have missed

1. captions to figures and table has been simpified

2. The manuscript has been proofreaded and grammatical or ortographic mistakes corrected.

3. The text has been considerably reformulated and hopefully ameliorated

4. The abstract has been shortened and made more adherent to journal guidelines

 

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript by Pace et al. reviews recent progress made in the field of auto-brewery syndrome (ABS). Although they provide a comprehensive overview of the causes of ABS and possible therapeutic strategies to overcome ABS, following comments should be addressed to enhance the manuscript’s readability:

Major comments:

1. Line 135-137: Rather than simply listing the risk factors for ABS, the authors should include at least one paragraph discussing these factors, citing recent publications that highlight their roles in inducing ABS.
2. Please italicize the scientific name(s) wherever mentioned and applicable (for example, in Figure 1).

Minor comments:

1. Line 53-55: “This rare condition is named in different ways in the literature, as for example gut fermentation syndrome, or  alcohol fermentation syndrome, or auto-brewery syndrome (ABS)”. The similar sentence is also written in the lines, 63-65. The authors should delete one of the two to avoid redundancy.

Comments on the Quality of English Language

My major concern is the language of the manuscript. There is a lot of inconsistency throughout in the manuscript. It would be better if the authors could do a language editing prior to submitting the revised version.

Author Response

Major comments:

1. Line 135-137: Rather than simply listing the risk factors for ABS, the authors should include at least one paragraph discussing these factors, citing recent publications that highlight their roles in inducing ABS.
2. Please italicize the scientific name(s) wherever mentioned and applicable (for example, in Figure 1).

Minor comments:

1. Line 53-55: “This rare condition is named in different ways in the literature, as for example gut fermentation syndrome, or  alcohol fermentation syndrome, or auto-brewery syndrome (ABS)”. The similar sentence is also written in the lines, 63-65. The authors should delete one of the two to avoid redundancy. 

Reply

1. Line 135-7- A new paragraph has now been inserted.
2. In the fig. 1, and where appropriate, the names of microbial species are in italics. 
3. Line 53-55- Done !

 

Reviewer 3 Report

Comments and Suggestions for Authors

Comments 

1. Summary looks AI generated content. Please modify some sentences.
2. Figure 1 graph is breaking in middle. give high resolution image.
3. Figure 3 is not clearly visible.
4. table 1 , data's are not arranged properly. modify with suitable references.
5. justify interaction with host physiological process.
6. Acknowledgement, data statement, funding sources , author's contribution are not given. so over all revision are recommended.

Comments on the Quality of English Language

English could be improved.

Author Response

Comments 

1. Summary looks AI generated content. Please modify some sentences.
2. Figure 1 graph is breaking in middle. give high resolution image.
3. Figure 3 is not clearly visible.
4. table 1 , data's are not arranged properly. modify with suitable references.
5. justify interaction with host physiological process.
6. Acknowledgement, data statement, funding sources , author's contribution are not given. so over all revision are recommended.

Reply

 

1. We did not use AI
2. The resolution of fig. 2 could not be improved
3. Idem for fig. 3
4. There was only a repetead mistake, ref. 5 should read 7. Now tht table is corrected.
5. This is now corrected in the text
6. Authors contribute equally to the paper. No funding sources were asked.

Reviewer 4 Report

Comments and Suggestions for Authors

Dear author A. Abu Issa, I have reviewed your review manuscript entitled "Ethanol-Producing Micro-Organisms of Human Gut: A Biological Phenomenon or a Disease?" with great interest. The study presents a timely and clinically relevant overview of endogenous ethanol production and its association with auto-brewery syndrome (ABS), particularly in the setting of metabolic disorders such as MAFLD and diabetes. The manuscript is well-structured, clearly written, and effectively outlines the microbiological mechanisms, diagnostic challenges, and potential therapeutic strategies related to ABS. However, several minor revisions are necessary before the manuscript can be considered for acceptance. The following comments should be addressed:

• The summary is clear, well-written, and effectively communicates the main points.
• The introduction addresses microbial involvement, detailing the fermentative actions of intestinal bacteria and fungus.
• You mention reviewing 5,937 articles to identify ethanol-producing microorganisms, but the manuscript lacks details on the search strategy, inclusion criteria, and sources consulted. Clarifying these elements would strengthen the credibility of the findings.
• To strengthen the manuscript, consider including a detailed list of the 61 bacterial species and 24 fungal species, either in the main document or as a supplementary file.
• Lactococcus lactis is typically considered a dairy bacterium rather than a natural inhabitant of the human intestine. Could you please clarify how this bacterium is involved in ethanol production within the gut?
• It is important to note that ethanol is a metabolite not naturally produced by Homo sapiens sapiens. Including references that support this statement would strengthen the manuscript and provide further clarity.
• The quality of Figure 3 should be improved, and the methods used to generate the graphs should also be revised for better clarity and precision.
• Please ensure that all species names are correctly italicized and consistently formatted in the revised manuscript.
• Numerous microorganisms are capable of producing ethanol in the gut, but Klebsiella pneumoniae and Saccharomyces cerevisiae are more prominently involved. Consider explaining the reason behind their higher ethanol output.
• Improving the quality and consistency of references throughout the manuscript is recommended. Furthermore, minor textual corrections are needed, such as changing “in-vivo” to the correct form “in vivo.”

Author Response

Dear author A. Abu Issa, I have reviewed your review manuscript entitled "Ethanol-Producing Micro-Organisms of Human Gut: A Biological Phenomenon or a Disease?" with great interest. The study presents a timely and clinically relevant overview of endogenous ethanol production and its association with auto-brewery syndrome (ABS), particularly in the setting of metabolic disorders such as MAFLD and diabetes. The manuscript is well-structured, clearly written, and effectively outlines the microbiological mechanisms, diagnostic challenges, and potential therapeutic strategies related to ABS. However, several minor revisions are necessary before the manuscript can be considered for acceptance. The following comments should be addressed:

• The summary is clear, well-written, and effectively communicates the main points.
• The introduction addresses microbial involvement, detailing the fermentative actions of intestinal bacteria and fungus.
• You mention reviewing 5,937 articles to identify ethanol-producing microorganisms, but the manuscript lacks details on the search strategy, inclusion criteria, and sources consulted. Clarifying these elements would strengthen the credibility of the findings.
• To strengthen the manuscript, consider including a detailed list of the 61 bacterial species and 24 fungal species, either in the main document or as a supplementary file.
• Lactococcus lactis is typically considered a dairy bacterium rather than a natural inhabitant of the human intestine. Could you please clarify how this bacterium is involved in ethanol production within the gut?
• It is important to note that ethanol is a metabolite not naturally produced by Homo sapiens sapiens. Including references that support this statement would strengthen the manuscript and provide further clarity.
• The quality of Figure 3 should be improved, and the methods used to generate the graphs should also be revised for better clarity and precision.
• Please ensure that all species names are correctly italicized and consistently formatted in the revised manuscript.
• Numerous microorganisms are capable of producing ethanol in the gut, but Klebsiella pneumoniae and Saccharomyces cerevisiae are more prominently involved. Consider explaining the reason behind their higher ethanol output.
• Improving the quality and consistency of references throughout the manuscript is recommended. Furthermore, minor textual corrections are needed, such as changing “in-vivo” to the correct form “in vivo.”

Reply

We thank this reviewer for the exhaustive revision of our paper.

Some issues have already been raised by other referees.

Concerning the original issues of Ref. 4:

The number of 5,937 articles retrieved refers to the work of Mbaye, not ours. The same applies for the list of 61 bacterial species and 24 fungal species found to be ethanol producers in vitro. The question of L. lactis again refers to paper by Mbaye et al. Ethanol production is universally known not to be in the domain of metabolic pathways by Homo sapiens. Sincerely, we do not think that a reference is necessary for this statement

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed all the comments.