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: 
17 Oct 2019
Reviewer's report:
The paper presents a systematic review and meta-analysis comparing short-chain
fatty acids (SCFA) and serotonin (5-HT) in subjects with IBS and healthy
controls.
The introduction is long but gives an informative rationale for performing the
meta-analysis.
The method section has been well described and follows the PRISMA principles
and uses adequate statistical software. The presentation of the results is good, but
the print quality of the figures are low and difficult to read on my copy of the
paper. 
The discussion is long and overlaps to some extent with the introduction. The
section about limitations deserves a better description. The most important
limitation is the lack of information about subgroups of IBS. The abnormalities
in SCFA and 5-HT probably vary between the subgroups. 5-HT might be high in
diarrhoea-predominant IBS (D-IBS) and low in constipation-predominant IBS
(C-IBS), and without knowledge of the subgroups the validity of the results
could be questioned. Subjects with D-IBS are often overrepresented in clinical
studies. This limitation is so important that it deserves being mentioned in the
abstract, e.g. "The study did not differentiate between subgroups of IBS". 5-HT
was measured in blood, but neither the analysis method nor if it was measured in
red blood cells, serum or plasma, was mentioned. 
5-HT in the mucosa could be a
better biomarker, but that was outside the scope of this paper. SCFA were
measured in faeces. Since most SCFA are absorbed in the colon, the results are
not representative for SCFA in other parts of the gastrointestinal tract. To
measure SCFA in faeces is convenient, and what most of us do and it is OK, but
it is a limitation.
Major concerns.
There are errors in the paper. In the study by Farup et al. (reference 27), patients
with IBS were not compared with healthy controls. The study included patients
with depression and unspecified neurological symptoms and compared patients
with and without IBS. When finding such errors, I wonder if the quality of the
paper is satisfactory. I have not looked through all referred papers. 
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.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
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 recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
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.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name
will be included on my report to the authors and, if the manuscript is accepted
for publication, my named report including any attachments I upload will be
posted on the website along with the authors' responses. 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/
). I understand that any comments
which I do not wish to be included in my named report can be included as
confidential comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
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: 
17 Oct 2019
Reviewer's report:
The paper presents a systematic review and meta-analysis comparing short-chain
fatty acids (SCFA) and serotonin (5-HT) in subjects with IBS and healthy
controls.
The introduction is long but gives an informative rationale for performing the
meta-analysis.
The method section has been well described and follows the PRISMA principles
and uses adequate statistical software. The presentation of the results is good, but
the print quality of the figures are low and difficult to read on my copy of the
paper. 
The discussion is long and overlaps to some extent with the introduction. The
section about limitations deserves a better description. The most important
limitation is the lack of information about subgroups of IBS. The abnormalities
in SCFA and 5-HT probably vary between the subgroups. 5-HT might be high in
diarrhoea-predominant IBS (D-IBS) and low in constipation-predominant IBS
(C-IBS), and without knowledge of the subgroups the validity of the results
could be questioned. Subjects with D-IBS are often overrepresented in clinical
studies. This limitation is so important that it deserves being mentioned in the
abstract, e.g. "The study did not differentiate between subgroups of IBS". 5-HT
was measured in blood, but neither the analysis method nor if it was measured in
red blood cells, serum or plasma, was mentioned. 
5-HT in the mucosa could be a
better biomarker, but that was outside the scope of this paper. SCFA were
measured in faeces. Since most SCFA are absorbed in the colon, the results are
not representative for SCFA in other parts of the gastrointestinal tract. To
measure SCFA in faeces is convenient, and what most of us do and it is OK, but
it is a limitation.
Major concerns.
There are errors in the paper. In the study by Farup et al. (reference 27), patients
with IBS were not compared with healthy controls. The study included patients
with depression and unspecified neurological symptoms and compared patients
with and without IBS. When finding such errors, I wonder if the quality of the
paper is satisfactory. I have not looked through all referred papers. 
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.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
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 recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
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.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name
will be included on my report to the authors and, if the manuscript is accepted
for publication, my named report including any attachments I upload will be
posted on the website along with the authors' responses. 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/
). I understand that any comments
which I do not wish to be included in my named report can be included as
confidential comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
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: 
17 Oct 2019
Reviewer's report:
The paper presents a systematic review and meta-analysis comparing short-chain
fatty acids (SCFA) and serotonin (5-HT) in subjects with IBS and healthy
controls.
The introduction is long but gives an informative rationale for performing the
meta-analysis.
The method section has been well described and follows the PRISMA principles
and uses adequate statistical software. The presentation of the results is good, but
the print quality of the figures are low and difficult to read on my copy of the
paper. 
The discussion is long and overlaps to some extent with the introduction. The
section about limitations deserves a better description. The most important
limitation is the lack of information about subgroups of IBS. The abnormalities
in SCFA and 5-HT probably vary between the subgroups. 5-HT might be high in
diarrhoea-predominant IBS (D-IBS) and low in constipation-predominant IBS
(C-IBS), and without knowledge of the subgroups the validity of the results
could be questioned. Subjects with D-IBS are often overrepresented in clinical
studies. This limitation is so important that it deserves being mentioned in the
abstract, e.g. "The study did not differentiate between subgroups of IBS". 5-HT
was measured in blood, but neither the analysis method nor if it was measured in
red blood cells, serum or plasma, was mentioned. 
5-HT in the mucosa could be a
better biomarker, but that was outside the scope of this paper. SCFA were
measured in faeces. Since most SCFA are absorbed in the colon, the results are
not representative for SCFA in other parts of the gastrointestinal tract. To
measure SCFA in faeces is convenient, and what most of us do and it is OK, but
it is a limitation.
Major concerns.
There are errors in the paper. In the study by Farup et al. (reference 27), patients
with IBS were not compared with healthy controls. The study included patients
with depression and unspecified neurological symptoms and compared patients
with and without IBS. When finding such errors, I wonder if the quality of the
paper is satisfactory. I have not looked through all referred papers. 
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.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
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 recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
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.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name
will be included on my report to the authors and, if the manuscript is accepted
for publication, my named report including any attachments I upload will be
posted on the website along with the authors' responses. 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/
). I understand that any comments
which I do not wish to be included in my named report can be included as
confidential comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant