Reviewer’s report
Title: 
Clinical efficacy of fecal microbiota transplantation for patients with small
intestinal bacterial overgrowth —A randomized, placebo-controlled trial study
Version: 
0 
Date: 
31 Jul 2020
Reviewer's report:
The manuscript by Fenghua Xu and colleagues on the Clinical efficacy of FMT
for SIBO is interesting and treats a topic, the use of FMT besides C. difficile
infections, that is presently highly discussed.
The manuscript, however, would highly benefit from a revision of few concepts
and a careful review of the references employed. Here follow the major points to
be clarified and corrected:
-Why do the authors refer to Donors (plural) but it looks like there is only one
donor in all the graphs of Figure 4? Similarly, in the discussion the authors admit
using only one donor (page 14).
-On page 1, line 34, please explain what is the meaning of "re-emerged". FMT
has been safely used, since long time, for recurrent C. difficile infection and just
recently has emerged as a therapeutic possibility for other GI disorders. 
-Similarly, on page 1, line 38: I would precise that has been safely used for
recurrent C. difficile infection and not any GI disease. I would suggest citing
these more recent manuscripts instead of reference 10 and 11:
https://pubmed.ncbi.nlm.nih.gov/31379333/
https://pubmed.ncbi.nlm.nih.gov/28087657/
-Page 1, line 44-48: This is not entirely true as we now know that there have
been sporadic reports of multi-drug resistant bacteria transferred through FMT,
and there could be a subtle low grade immune response to the new bacterial
community that has been introduced. I would modify the phrase to reflect that
FMT is mostly safe and does not elicit the immune rejection that a transplanted
organ could elicit.
-On page 23 there is a paragraph on outcomes of LBHT which appears to be
disconnected from the tables.
-What is the difference between Figure 4B and 4C? Just the inclusion of post-
FMT and post-placebo?
-Please refrain from using the term "flora" or "microflora", as this term is not
correct. Flora refers to vegetation and here the term to be used is microbiota or
microbial community.
-Please correct microbiotas to microbiota (which is already plural).
-What are the P values of the results shown in Figure 4E? Please add in the text
on page 10 and add significance to the figure.
-What is the meaning of the correlation plot shown on Figure 4F? There is no
mention of it anywhere and appears to add little information.
-What do the authors mean with "...a different set rate" on page 11 line 7?
-Page 11, lines 23-29. Please modify the phrase as is not completely clear as is.
Please use one of the above mentioned references for FMT.
-Page 11, lines29-31, please add references.
-Page 11, lines37-39, please add that this refers to C. difficile context.
-Reference 29 is actually 28.
-Page 12, reference 30 should be substituted by one that refers to breath testing
as diagnostic test for SIBO.
-Page 12, line 41. The authors should precise that is not one capsule but 16. How
did the patients react to having to ingest 16 capsules all in one setting?
-Please correct Reference 34. This reference appears to be repeated and is # 15.
-Page 12, lines 49-55: Please rephrase "...to "standardize" the establishment of
the library of fecal bacteria, indicating the new direction of treatment."
-Page 13, lines 5-13. Did the authors quantify the microbiota? There is no
mention in the study, there is only mention of characterization of the donor
microbiota. How did the authors establish the "reduction of dead flora"? What
does it mean to "increase the application scope"?
-Page 13, line 32. Please substitute the references with ones that refer to
antibiotic treatment for SIBO.
-Page 13, reference 38 does not seem to refer to a connection between SIBO and
dysbiosis. Isn't it SIBO already a clear example of dysbiosis?
-Page 13, line 59-Page 14 line 5. Please rephrase as "probiotic preparations such
as probiotics" is a bit redundant.
-Page 14, lines 5-14. Please rephrase as is not clear and the part "especially
gradually developed FMT, which has high curative effects for similar reasons"
appears to be disconnected from the rest. In addition FMT is not a probiotic
preparation.
-Page 14, line 19: "...which cannot optimally restore the gut microbiota barrier..."
What are the authors refer to here for microbiota barrier? To the protective effect
of a homeostatic gut microbiota? Please correct accordingly.
-Page 14, lines 34-40. This phrase could be joined with the previous phrase on
page 12-page 13 describing the advantage of this FMT technique over others.
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Yes
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
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)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Clinical efficacy of fecal microbiota transplantation for patients with small
intestinal bacterial overgrowth —A randomized, placebo-controlled trial study
Version: 
0 
Date: 
31 Jul 2020
Reviewer's report:
The manuscript by Fenghua Xu and colleagues on the Clinical efficacy of FMT
for SIBO is interesting and treats a topic, the use of FMT besides C. difficile
infections, that is presently highly discussed.
The manuscript, however, would highly benefit from a revision of few concepts
and a careful review of the references employed. Here follow the major points to
be clarified and corrected:
-Why do the authors refer to Donors (plural) but it looks like there is only one
donor in all the graphs of Figure 4? Similarly, in the discussion the authors admit
using only one donor (page 14).
-On page 1, line 34, please explain what is the meaning of "re-emerged". FMT
has been safely used, since long time, for recurrent C. difficile infection and just
recently has emerged as a therapeutic possibility for other GI disorders. 
-Similarly, on page 1, line 38: I would precise that has been safely used for
recurrent C. difficile infection and not any GI disease. I would suggest citing
these more recent manuscripts instead of reference 10 and 11:
https://pubmed.ncbi.nlm.nih.gov/31379333/
https://pubmed.ncbi.nlm.nih.gov/28087657/
-Page 1, line 44-48: This is not entirely true as we now know that there have
been sporadic reports of multi-drug resistant bacteria transferred through FMT,
and there could be a subtle low grade immune response to the new bacterial
community that has been introduced. I would modify the phrase to reflect that
FMT is mostly safe and does not elicit the immune rejection that a transplanted
organ could elicit.
-On page 23 there is a paragraph on outcomes of LBHT which appears to be
disconnected from the tables.
-What is the difference between Figure 4B and 4C? Just the inclusion of post-
FMT and post-placebo?
-Please refrain from using the term "flora" or "microflora", as this term is not
correct. Flora refers to vegetation and here the term to be used is microbiota or
microbial community.
-Please correct microbiotas to microbiota (which is already plural).
-What are the P values of the results shown in Figure 4E? Please add in the text
on page 10 and add significance to the figure.
-What is the meaning of the correlation plot shown on Figure 4F? There is no
mention of it anywhere and appears to add little information.
-What do the authors mean with "...a different set rate" on page 11 line 7?
-Page 11, lines 23-29. Please modify the phrase as is not completely clear as is.
Please use one of the above mentioned references for FMT.
-Page 11, lines29-31, please add references.
-Page 11, lines37-39, please add that this refers to C. difficile context.
-Reference 29 is actually 28.
-Page 12, reference 30 should be substituted by one that refers to breath testing
as diagnostic test for SIBO.
-Page 12, line 41. The authors should precise that is not one capsule but 16. How
did the patients react to having to ingest 16 capsules all in one setting?
-Please correct Reference 34. This reference appears to be repeated and is # 15.
-Page 12, lines 49-55: Please rephrase "...to "standardize" the establishment of
the library of fecal bacteria, indicating the new direction of treatment."
-Page 13, lines 5-13. Did the authors quantify the microbiota? There is no
mention in the study, there is only mention of characterization of the donor
microbiota. How did the authors establish the "reduction of dead flora"? What
does it mean to "increase the application scope"?
-Page 13, line 32. Please substitute the references with ones that refer to
antibiotic treatment for SIBO.
-Page 13, reference 38 does not seem to refer to a connection between SIBO and
dysbiosis. Isn't it SIBO already a clear example of dysbiosis?
-Page 13, line 59-Page 14 line 5. Please rephrase as "probiotic preparations such
as probiotics" is a bit redundant.
-Page 14, lines 5-14. Please rephrase as is not clear and the part "especially
gradually developed FMT, which has high curative effects for similar reasons"
appears to be disconnected from the rest. In addition FMT is not a probiotic
preparation.
-Page 14, line 19: "...which cannot optimally restore the gut microbiota barrier..."
What are the authors refer to here for microbiota barrier? To the protective effect
of a homeostatic gut microbiota? Please correct accordingly.
-Page 14, lines 34-40. This phrase could be joined with the previous phrase on
page 12-page 13 describing the advantage of this FMT technique over others.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
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
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)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Clinical efficacy of fecal microbiota transplantation for patients with small
intestinal bacterial overgrowth —A randomized, placebo-controlled trial study
Version: 
0 
Date: 
31 Jul 2020
Reviewer's report:
The manuscript by Fenghua Xu and colleagues on the Clinical efficacy of FMT
for SIBO is interesting and treats a topic, the use of FMT besides C. difficile
infections, that is presently highly discussed.
The manuscript, however, would highly benefit from a revision of few concepts
and a careful review of the references employed. Here follow the major points to
be clarified and corrected:
-Why do the authors refer to Donors (plural) but it looks like there is only one
donor in all the graphs of Figure 4? Similarly, in the discussion the authors admit
using only one donor (page 14).
-On page 1, line 34, please explain what is the meaning of "re-emerged". FMT
has been safely used, since long time, for recurrent C. difficile infection and just
recently has emerged as a therapeutic possibility for other GI disorders. 
-Similarly, on page 1, line 38: I would precise that has been safely used for
recurrent C. difficile infection and not any GI disease. I would suggest citing
these more recent manuscripts instead of reference 10 and 11:
https://pubmed.ncbi.nlm.nih.gov/31379333/
https://pubmed.ncbi.nlm.nih.gov/28087657/
-Page 1, line 44-48: This is not entirely true as we now know that there have
been sporadic reports of multi-drug resistant bacteria transferred through FMT,
and there could be a subtle low grade immune response to the new bacterial
community that has been introduced. I would modify the phrase to reflect that
FMT is mostly safe and does not elicit the immune rejection that a transplanted
organ could elicit.
-On page 23 there is a paragraph on outcomes of LBHT which appears to be
disconnected from the tables.
-What is the difference between Figure 4B and 4C? Just the inclusion of post-
FMT and post-placebo?
-Please refrain from using the term "flora" or "microflora", as this term is not
correct. Flora refers to vegetation and here the term to be used is microbiota or
microbial community.
-Please correct microbiotas to microbiota (which is already plural).
-What are the P values of the results shown in Figure 4E? Please add in the text
on page 10 and add significance to the figure.
-What is the meaning of the correlation plot shown on Figure 4F? There is no
mention of it anywhere and appears to add little information.
-What do the authors mean with "...a different set rate" on page 11 line 7?
-Page 11, lines 23-29. Please modify the phrase as is not completely clear as is.
Please use one of the above mentioned references for FMT.
-Page 11, lines29-31, please add references.
-Page 11, lines37-39, please add that this refers to C. difficile context.
-Reference 29 is actually 28.
-Page 12, reference 30 should be substituted by one that refers to breath testing
as diagnostic test for SIBO.
-Page 12, line 41. The authors should precise that is not one capsule but 16. How
did the patients react to having to ingest 16 capsules all in one setting?
-Please correct Reference 34. This reference appears to be repeated and is # 15.
-Page 12, lines 49-55: Please rephrase "...to "standardize" the establishment of
the library of fecal bacteria, indicating the new direction of treatment."
-Page 13, lines 5-13. Did the authors quantify the microbiota? There is no
mention in the study, there is only mention of characterization of the donor
microbiota. How did the authors establish the "reduction of dead flora"? What
does it mean to "increase the application scope"?
-Page 13, line 32. Please substitute the references with ones that refer to
antibiotic treatment for SIBO.
-Page 13, reference 38 does not seem to refer to a connection between SIBO and
dysbiosis. Isn't it SIBO already a clear example of dysbiosis?
-Page 13, line 59-Page 14 line 5. Please rephrase as "probiotic preparations such
as probiotics" is a bit redundant.
-Page 14, lines 5-14. Please rephrase as is not clear and the part "especially
gradually developed FMT, which has high curative effects for similar reasons"
appears to be disconnected from the rest. In addition FMT is not a probiotic
preparation.
-Page 14, line 19: "...which cannot optimally restore the gut microbiota barrier..."
What are the authors refer to here for microbiota barrier? To the protective effect
of a homeostatic gut microbiota? Please correct accordingly.
-Page 14, lines 34-40. This phrase could be joined with the previous phrase on
page 12-page 13 describing the advantage of this FMT technique over others.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
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
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)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant