Title: Causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study
Version: 2 Date: 13 Apr 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is the review of a manuscript titled "Causal relationship
between gut microbiota and constipation: a two-sample Mendelian randomization study". In
this MS,  there relationships between specific gut microbiota taxa and constipation were studied
using MR. This is a good quality study, well written (except Abstract, which seem to be
added later, when the body of MS was finished separately and went through some polishing.
On scientifics merits: it deserve publishing, with two additions. 1. Age is a common factor
mediating both microbiota abundancies and constipation phenotypes. If mediation analysis for
any reason not possible, authors should, at the very least, mention this in discussion. 2. Another
point that "protection against constipation" in this study was much more pronounced than the
"promotion of constipation". This observation should be discussed, one can think of a few
biological hypothesis to explore.
REQUESTED REVISIONS:
There is a need for some grammar revision, especially in abstract. For example, "As one of
the most common gastrointestinal disorders, recent study has shown that dysfunction in the
gut microbiota might lead to constipation. However, the causality between the gut microbiota
and constipation is unclear." should be edited into something like " One of the most common
gastrointestinal disorders, constipation, may result from the dysfunction in the gut microbiota.
However, the causal relationships between certain taxa of gut bacteria and constipation are not
yet mapped." I also recommend citing recent review, it also have some discussion on a role
of certain taxa in constipation https://pubmed.ncbi.nlm.nih.gov/38446304/. Also, authors need
to emphasize that MR evaluates only GENETIC component of a certain exposure (i.e it will
evaluate a role of genomic variants influencing abundancies of certain microbes on constipation,
but will not be able to evaluate actual changes made in these abundancies introduced by inherent
differences in lifestyle).
ADDITIONAL REQUESTS/SUGGESTIONS:
one more proofread will be need after changes to Discussion
Title: Causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study
Version: 2 Date: 13 Apr 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is the review of a manuscript titled "Causal relationship
between gut microbiota and constipation: a two-sample Mendelian randomization study". In
this MS,  there relationships between specific gut microbiota taxa and constipation were studied
using MR. This is a good quality study, well written (except Abstract, which seem to be
added later, when the body of MS was finished separately and went through some polishing.
On scientifics merits: it deserve publishing, with two additions. 1. Age is a common factor
mediating both microbiota abundancies and constipation phenotypes. If mediation analysis for
any reason not possible, authors should, at the very least, mention this in discussion. 2. Another
point that "protection against constipation" in this study was much more pronounced than the
"promotion of constipation". This observation should be discussed, one can think of a few
biological hypothesis to explore.
REQUESTED REVISIONS:
There is a need for some grammar revision, especially in abstract. For example, "As one of
the most common gastrointestinal disorders, recent study has shown that dysfunction in the
gut microbiota might lead to constipation. However, the causality between the gut microbiota
and constipation is unclear." should be edited into something like " One of the most common
gastrointestinal disorders, constipation, may result from the dysfunction in the gut microbiota.
However, the causal relationships between certain taxa of gut bacteria and constipation are not
yet mapped." I also recommend citing recent review, it also have some discussion on a role
of certain taxa in constipation https://pubmed.ncbi.nlm.nih.gov/38446304/. Also, authors need
to emphasize that MR evaluates only GENETIC component of a certain exposure (i.e it will
evaluate a role of genomic variants influencing abundancies of certain microbes on constipation,
but will not be able to evaluate actual changes made in these abundancies introduced by inherent
differences in lifestyle).
ADDITIONAL REQUESTS/SUGGESTIONS:
one more proofread will be need after changes to Discussion
Please review this paper.
user
Title: Causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study
Version: 2 Date: 13 Apr 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is the review of a manuscript titled "Causal relationship
between gut microbiota and constipation: a two-sample Mendelian randomization study". In
this MS,  there relationships between specific gut microbiota taxa and constipation were studied
using MR. This is a good quality study, well written (except Abstract, which seem to be
added later, when the body of MS was finished separately and went through some polishing.
On scientifics merits: it deserve publishing, with two additions. 1. Age is a common factor
mediating both microbiota abundancies and constipation phenotypes. If mediation analysis for
any reason not possible, authors should, at the very least, mention this in discussion. 2. Another
point that "protection against constipation" in this study was much more pronounced than the
"promotion of constipation". This observation should be discussed, one can think of a few
biological hypothesis to explore.
REQUESTED REVISIONS:
There is a need for some grammar revision, especially in abstract. For example, "As one of
the most common gastrointestinal disorders, recent study has shown that dysfunction in the
gut microbiota might lead to constipation. However, the causality between the gut microbiota
and constipation is unclear." should be edited into something like " One of the most common
gastrointestinal disorders, constipation, may result from the dysfunction in the gut microbiota.
However, the causal relationships between certain taxa of gut bacteria and constipation are not
yet mapped." I also recommend citing recent review, it also have some discussion on a role
of certain taxa in constipation https://pubmed.ncbi.nlm.nih.gov/38446304/. Also, authors need
to emphasize that MR evaluates only GENETIC component of a certain exposure (i.e it will
evaluate a role of genomic variants influencing abundancies of certain microbes on constipation,
but will not be able to evaluate actual changes made in these abundancies introduced by inherent
differences in lifestyle).
ADDITIONAL REQUESTS/SUGGESTIONS:
one more proofread will be need after changes to Discussion
assistant