Reviewer’s report
Title: 
Alterations in short-chain fatty acids and serotonin in irritable bowel
syndrome: a systematic review and meta-analysis
Version: 
1 
Date: 
15 May 2020
Reviewer's report:
It is not new that "alterations" of 5-HT and SCFAs in IBS patients may be
involved, through the 
brain-gut-microbiota axis, in the pathophysiology of IBS.
Unfortunately there are conflicting results (Increase? Decrease? 
Heterogeneity of
analyzed samples, etc.) 
The aim of the study is to evaluate the papers dealing with this complex issue
through a metanalysis, showing: 
- serotonin alterations in patients with IBS 
- short chain fatty acid alterations in patients with IBS 
- the role of serotonin and SCFAs in the brain-gut-microbiota axis 
Abstract 
It is clearly written but the "potential role of SCFAs and 5-HT in the BGM axis"
is not treated as an objective of the study. 
Introduction. 
The authors should review the manuscript organization; particularly the
paragraphs dedicated to the explanation of the brain-gut-microbiota axis. There
is no clear logical sequence and there are frequent repetitions regarding the role
of serotonin and microbiota. Adding a figure to explain the bi-directional
interplay of the BGM axis, which is often mentioned, might help. In addition,
one issue that is a bit confusing is that we do not understand what is meant by
"alterations of SCFAs and 5-HT"; it is a too general term and the authors should
clarify if they are talking about plasma, faecal, urinary, tissue, etc. changes
Materials and methods 
The description is accurate but the flow chart describing the selection of items,
present as additional file, could be profitably inserted. 
Results 
They are consistent with the first two objectives of the study. 
A table showing the results of the 5-HT and SCFAs measurements carried on in
the studies under review could help.
Discussion
Some of the issues have already been extensively discussed in the introduction
so they could be redundant.
Moreover, the authors do not adequately discuss the papers dealing with the third
objective (role of SCFAs and 5-HT in the BMG axis) 
English is worthy of some syntax corrections in the introduction and the
discussion. Overall the paper is written in an understandable style. 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
None
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Reviewer’s report
Title: 
Alterations in short-chain fatty acids and serotonin in irritable bowel
syndrome: a systematic review and meta-analysis
Version: 
1 
Date: 
15 May 2020
Reviewer's report:
It is not new that "alterations" of 5-HT and SCFAs in IBS patients may be
involved, through the 
brain-gut-microbiota axis, in the pathophysiology of IBS.
Unfortunately there are conflicting results (Increase? Decrease? 
Heterogeneity of
analyzed samples, etc.) 
The aim of the study is to evaluate the papers dealing with this complex issue
through a metanalysis, showing: 
- serotonin alterations in patients with IBS 
- short chain fatty acid alterations in patients with IBS 
- the role of serotonin and SCFAs in the brain-gut-microbiota axis 
Abstract 
It is clearly written but the "potential role of SCFAs and 5-HT in the BGM axis"
is not treated as an objective of the study. 
Introduction. 
The authors should review the manuscript organization; particularly the
paragraphs dedicated to the explanation of the brain-gut-microbiota axis. There
is no clear logical sequence and there are frequent repetitions regarding the role
of serotonin and microbiota. Adding a figure to explain the bi-directional
interplay of the BGM axis, which is often mentioned, might help. In addition,
one issue that is a bit confusing is that we do not understand what is meant by
"alterations of SCFAs and 5-HT"; it is a too general term and the authors should
clarify if they are talking about plasma, faecal, urinary, tissue, etc. changes
Materials and methods 
The description is accurate but the flow chart describing the selection of items,
present as additional file, could be profitably inserted. 
Results 
They are consistent with the first two objectives of the study. 
A table showing the results of the 5-HT and SCFAs measurements carried on in
the studies under review could help.
Discussion
Some of the issues have already been extensively discussed in the introduction
so they could be redundant.
Moreover, the authors do not adequately discuss the papers dealing with the third
objective (role of SCFAs and 5-HT in the BMG axis) 
English is worthy of some syntax corrections in the introduction and the
discussion. Overall the paper is written in an understandable style. 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
None
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Please review this paper.
user
Reviewer’s report
Title: 
Alterations in short-chain fatty acids and serotonin in irritable bowel
syndrome: a systematic review and meta-analysis
Version: 
1 
Date: 
15 May 2020
Reviewer's report:
It is not new that "alterations" of 5-HT and SCFAs in IBS patients may be
involved, through the 
brain-gut-microbiota axis, in the pathophysiology of IBS.
Unfortunately there are conflicting results (Increase? Decrease? 
Heterogeneity of
analyzed samples, etc.) 
The aim of the study is to evaluate the papers dealing with this complex issue
through a metanalysis, showing: 
- serotonin alterations in patients with IBS 
- short chain fatty acid alterations in patients with IBS 
- the role of serotonin and SCFAs in the brain-gut-microbiota axis 
Abstract 
It is clearly written but the "potential role of SCFAs and 5-HT in the BGM axis"
is not treated as an objective of the study. 
Introduction. 
The authors should review the manuscript organization; particularly the
paragraphs dedicated to the explanation of the brain-gut-microbiota axis. There
is no clear logical sequence and there are frequent repetitions regarding the role
of serotonin and microbiota. Adding a figure to explain the bi-directional
interplay of the BGM axis, which is often mentioned, might help. In addition,
one issue that is a bit confusing is that we do not understand what is meant by
"alterations of SCFAs and 5-HT"; it is a too general term and the authors should
clarify if they are talking about plasma, faecal, urinary, tissue, etc. changes
Materials and methods 
The description is accurate but the flow chart describing the selection of items,
present as additional file, could be profitably inserted. 
Results 
They are consistent with the first two objectives of the study. 
A table showing the results of the 5-HT and SCFAs measurements carried on in
the studies under review could help.
Discussion
Some of the issues have already been extensively discussed in the introduction
so they could be redundant.
Moreover, the authors do not adequately discuss the papers dealing with the third
objective (role of SCFAs and 5-HT in the BMG axis) 
English is worthy of some syntax corrections in the introduction and the
discussion. Overall the paper is written in an understandable style. 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
None
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
assistant