Reviewer’s report
Title: 
Characterization of Gut Microbiota Associated with Clinical Parameters in
Intrahepatic Cholestasis of Pregnancy
Version: 
0 
Date: 
16 Jan 2020
Reviewer: 
Jian-She Wang
Reviewer's report:
Li et al, in manuscript "characterization of gut microbiota associated with
clinical parameters in intrahepatic cholestasis of pregnant (ICP) patients"
describied the gut microbiota difference of ICP from normal preganancy as
controls. Generally, the manuscript is not well prepared in consideration of the
table format and lots of writting errors.
Major:
1. To observe the microbiota changes, if a longitudinal obeservation can be add,
that will be much better than only a cross-section study.
2. The last sentence of the conclusion in the Abstract, "These alterations may be
... in the progression of ICP" is not supported by the results listed in the abstract.
3. In the last paragraph of the background, Line 13-19,"we hypothesized that
several ...be inhibited in patients with ICP". What is the rational for this
hypothesis?
4. There is a difference in gestional age between the two groups. Though the
authors stated that the microbiota does not change quite a lot in pregnancy, some
publications (like Koren O, Goodrich J. K, Cullender T. C, et al. Host
remodeling of the gut microbiome and metabolic changes during pregnancy[J].
Cell. 2012. 150(3): 470-80) do observed dramatic changes in gut microbiota
during the pregancy.
5. please give an explanation why the ALT associated OTUs are different from
AST associated OTUs; Same for Tbil and Dbile.
minor:
1. In Abstract, Background, Line 7-8, "elevated liver functions", what do you
refer to? ALT or AST, OR Alb, OR bilirubin, TBA? Liver function is a broad
concept. Please specify. 
2. In Abstrct, Methods, Line 20, "31 unafflicted control patients". Usually we
may not call a pregnancy women as patient. Same problem is seen throughout
the manuscript.
3, In study participants, line 42, "ICP was diagnosed and classified...". I do not
see how ICP was specified in the following contents.
4. in the Sampling, line 11, I'd suggest that GGT be also included in the
biochemical parameters, as well ALT/AST, Tbil/Dbil.
5. In the results, Study Subject Characteristics section, line 53, "of bile, ALT,
AST,...". Do you mean total bile acid by bile? or what other doyou mean by bile?
6. The format of Table 1 needs to be changed to a format that consistent to the
Journal's requirments.
7. Many type errors in the manuscript, please ckeck carefully.
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:
Not suitable for publication unless extensively edited
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: 
Characterization of Gut Microbiota Associated with Clinical Parameters in
Intrahepatic Cholestasis of Pregnancy
Version: 
0 
Date: 
16 Jan 2020
Reviewer: 
Jian-She Wang
Reviewer's report:
Li et al, in manuscript "characterization of gut microbiota associated with
clinical parameters in intrahepatic cholestasis of pregnant (ICP) patients"
describied the gut microbiota difference of ICP from normal preganancy as
controls. Generally, the manuscript is not well prepared in consideration of the
table format and lots of writting errors.
Major:
1. To observe the microbiota changes, if a longitudinal obeservation can be add,
that will be much better than only a cross-section study.
2. The last sentence of the conclusion in the Abstract, "These alterations may be
... in the progression of ICP" is not supported by the results listed in the abstract.
3. In the last paragraph of the background, Line 13-19,"we hypothesized that
several ...be inhibited in patients with ICP". What is the rational for this
hypothesis?
4. There is a difference in gestional age between the two groups. Though the
authors stated that the microbiota does not change quite a lot in pregnancy, some
publications (like Koren O, Goodrich J. K, Cullender T. C, et al. Host
remodeling of the gut microbiome and metabolic changes during pregnancy[J].
Cell. 2012. 150(3): 470-80) do observed dramatic changes in gut microbiota
during the pregancy.
5. please give an explanation why the ALT associated OTUs are different from
AST associated OTUs; Same for Tbil and Dbile.
minor:
1. In Abstract, Background, Line 7-8, "elevated liver functions", what do you
refer to? ALT or AST, OR Alb, OR bilirubin, TBA? Liver function is a broad
concept. Please specify. 
2. In Abstrct, Methods, Line 20, "31 unafflicted control patients". Usually we
may not call a pregnancy women as patient. Same problem is seen throughout
the manuscript.
3, In study participants, line 42, "ICP was diagnosed and classified...". I do not
see how ICP was specified in the following contents.
4. in the Sampling, line 11, I'd suggest that GGT be also included in the
biochemical parameters, as well ALT/AST, Tbil/Dbil.
5. In the results, Study Subject Characteristics section, line 53, "of bile, ALT,
AST,...". Do you mean total bile acid by bile? or what other doyou mean by bile?
6. The format of Table 1 needs to be changed to a format that consistent to the
Journal's requirments.
7. Many type errors in the manuscript, please ckeck carefully.
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:
Not suitable for publication unless extensively edited
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: 
Characterization of Gut Microbiota Associated with Clinical Parameters in
Intrahepatic Cholestasis of Pregnancy
Version: 
0 
Date: 
16 Jan 2020
Reviewer: 
Jian-She Wang
Reviewer's report:
Li et al, in manuscript "characterization of gut microbiota associated with
clinical parameters in intrahepatic cholestasis of pregnant (ICP) patients"
describied the gut microbiota difference of ICP from normal preganancy as
controls. Generally, the manuscript is not well prepared in consideration of the
table format and lots of writting errors.
Major:
1. To observe the microbiota changes, if a longitudinal obeservation can be add,
that will be much better than only a cross-section study.
2. The last sentence of the conclusion in the Abstract, "These alterations may be
... in the progression of ICP" is not supported by the results listed in the abstract.
3. In the last paragraph of the background, Line 13-19,"we hypothesized that
several ...be inhibited in patients with ICP". What is the rational for this
hypothesis?
4. There is a difference in gestional age between the two groups. Though the
authors stated that the microbiota does not change quite a lot in pregnancy, some
publications (like Koren O, Goodrich J. K, Cullender T. C, et al. Host
remodeling of the gut microbiome and metabolic changes during pregnancy[J].
Cell. 2012. 150(3): 470-80) do observed dramatic changes in gut microbiota
during the pregancy.
5. please give an explanation why the ALT associated OTUs are different from
AST associated OTUs; Same for Tbil and Dbile.
minor:
1. In Abstract, Background, Line 7-8, "elevated liver functions", what do you
refer to? ALT or AST, OR Alb, OR bilirubin, TBA? Liver function is a broad
concept. Please specify. 
2. In Abstrct, Methods, Line 20, "31 unafflicted control patients". Usually we
may not call a pregnancy women as patient. Same problem is seen throughout
the manuscript.
3, In study participants, line 42, "ICP was diagnosed and classified...". I do not
see how ICP was specified in the following contents.
4. in the Sampling, line 11, I'd suggest that GGT be also included in the
biochemical parameters, as well ALT/AST, Tbil/Dbil.
5. In the results, Study Subject Characteristics section, line 53, "of bile, ALT,
AST,...". Do you mean total bile acid by bile? or what other doyou mean by bile?
6. The format of Table 1 needs to be changed to a format that consistent to the
Journal's requirments.
7. Many type errors in the manuscript, please ckeck carefully.
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:
Not suitable for publication unless extensively edited
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