Title: Causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study
Version: 6 Date: 18 May 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (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 sufficient 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?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is a repeat review of the revised manuscript
"The causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study ", which was, indeed, much improved after  revision, with added material
in Discussion and the small changes done throughout. Please do further set of the small changes
outlined below (this will not require re-reviewing": 1) in the first paragraph of Abstract :"....with
recent observational studies implicating dysfunction of the gut microbiota IN constipation.
While observational studies indicate a relationship, causal  connection between microbial
composition and constipation remain unclear. " 2) in the following phrase, change the grammar
tense: "Liu et al [15] demonstrated that constipation significantly changes the diversity of
intestinal microbial communities and affects the fecal metabolites". 3) In ".... the two protective
bacteria, demonstrate a substantially stronger effect..." remove comma. 4)  "...the gut microbiota
of the Japanese population differs markedly from THAT OF other populations [48]".
ADDITIONAL REQUESTS/SUGGESTIONS:
This is manuscript of good quality. Please see small grammar/ flow changes requested above.
MS may be published without the need of further reviewing, after changes made
Title: Causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study
Version: 6 Date: 18 May 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (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 sufficient 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?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is a repeat review of the revised manuscript
"The causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study ", which was, indeed, much improved after  revision, with added material
in Discussion and the small changes done throughout. Please do further set of the small changes
outlined below (this will not require re-reviewing": 1) in the first paragraph of Abstract :"....with
recent observational studies implicating dysfunction of the gut microbiota IN constipation.
While observational studies indicate a relationship, causal  connection between microbial
composition and constipation remain unclear. " 2) in the following phrase, change the grammar
tense: "Liu et al [15] demonstrated that constipation significantly changes the diversity of
intestinal microbial communities and affects the fecal metabolites". 3) In ".... the two protective
bacteria, demonstrate a substantially stronger effect..." remove comma. 4)  "...the gut microbiota
of the Japanese population differs markedly from THAT OF other populations [48]".
ADDITIONAL REQUESTS/SUGGESTIONS:
This is manuscript of good quality. Please see small grammar/ flow changes requested above.
MS may be published without the need of further reviewing, after changes made
Please review this paper.
user
Title: Causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study
Version: 6 Date: 18 May 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (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 sufficient 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?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is a repeat review of the revised manuscript
"The causal relationship between gut microbiota and constipation: a two-sample Mendelian
randomization study ", which was, indeed, much improved after  revision, with added material
in Discussion and the small changes done throughout. Please do further set of the small changes
outlined below (this will not require re-reviewing": 1) in the first paragraph of Abstract :"....with
recent observational studies implicating dysfunction of the gut microbiota IN constipation.
While observational studies indicate a relationship, causal  connection between microbial
composition and constipation remain unclear. " 2) in the following phrase, change the grammar
tense: "Liu et al [15] demonstrated that constipation significantly changes the diversity of
intestinal microbial communities and affects the fecal metabolites". 3) In ".... the two protective
bacteria, demonstrate a substantially stronger effect..." remove comma. 4)  "...the gut microbiota
of the Japanese population differs markedly from THAT OF other populations [48]".
ADDITIONAL REQUESTS/SUGGESTIONS:
This is manuscript of good quality. Please see small grammar/ flow changes requested above.
MS may be published without the need of further reviewing, after changes made
assistant