Review for 10.1186/s12876-021-01630-x (2021)

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: 
27 Aug 2020
Reviewer's report:
The manuscript describes a RCT examining FMT on outcomes of SIBO.
Abstract
It is noted that an observational target was the abdominal CT scan. Was this
done on only one participant or was only one notable patient described? Please
delete here and elsewhere in the methods and the results as this outcome was not
evaluated for the participants as a whole or a subsample. 
Page 2 Line 27/28 "intestinal" should this be "fecal" ? 
Delete "The CT scan of the abdomen demonstrated the disappearance of
intestinal
pneumatosis" as this was completed on only one patient.
Background
Page 3 Line 9 - Is translocation required though? Please reference. 
Statement "The presence of SIBO has influences on the progression and
prognosis of
the above mentioned diseases, both directly and indirectly." Explanation and
reference needed. 
Page 3 Line 27/28 reference is needed for the 37.5%
Page 3 Line 30-31 The sentence "Beyond that, probiotics can be used to help
restore
the gut microbial ecosystem, with a curative effect of 62.8% [9]" does not
appropriately represent the findings of the meta-analysis referenced as 62.8% I
believe included trials with antibiotics. If probiotics did have a curative effect of
62.8% would it not suggest that FMT is not needed as probiotics, with their
strong safety record, could be given instead? 
Lines 34-40 Please clarify that this specifically refers to recurrent C. diff
infection vs a generality of GI disease.
Methods
Pg 5 Please delete the names of the investigators in lines 15-17. 
Page 5 Please provide an explanation/clarification for the following line 50-54
"cases where the authors were unable to determine whether the inspection results
or incomplete data affected the judgment of the results; and cases in which
serious adverse events occurred. This suggests that there were more participants
than the 55 listed in the flow diagram. 
The "Donors" section is notably plural vs singular in the description. However,
in the limitations it is stated it is stated that there was only one donor. 
Please
clarify. 
GSRS - pg 8. GSRS tool - please revise description as the each item of the
GSRS is scored from 1-7 not 0-3. The GSRS is presented as a total syndrome
score but instead, the mean scores of each of the 5 domains would be much more
informative and the tool is validated as such. Please revise the analysis and
results using the GSRS syndromes vs. total score. Or is it a specific SIBO-
GSRS? Please reference in methods if so.
Please delete the description of the one patient CT scan as explained above.
Lines 7-17 pg 10.
Microbiota analysis - details of collection and storage of samples are missing
and steps of analysis are brief and are thus not reproducible as described. Please
add references if previously reported in detail or if not, please add details. Also,
additional details of statistics are needed. 
Please revise to microbiome vs "microbiotas" as DNA is being described. 
Pg 10 Line 47 "intestinal types" not sure what this is referring to. 
Pg 10 line 50-53- What different levels? Were there differences beyond
Bacteroides? 
Pg 11 line 5-7 is this statement specifically referring to SIBO? 
*Results of microbiome analysis states that donors (plural) had higher
microbiota diversity than patients but there was only one donor in the figure.
Does the stats analysis in Fig 4 A include the 4 groups excluding the donor? 
Fig
4 C - I do not see any clear clustering. Fig 4 D is too small to decipher. I would
recommend the Fig 4 E present the placebo also - this figure includes family and
order not only genus as stated. Why was this set of taxa chosen for this
comparison? The text description of the results refers to donors vs donor in
figures. 
The discussion emphasizes why the methods were chosen vs. an in-depth
discussion of findings and potential mechanisms. Importantly, authors have
argued that FMT has the capacity to alter the microbiome compared to
probiotics, however, only Bacteriodes was increased and this was possibly by
chance as methods/stats do not clearly indicate how multiple comparisons were
taken into consideration/adjusted for. What then contributed to the increase in
alpha diversity? How does fecal microbiota relate back to symptoms of SIBO?
This needs to be discussed 
Please revise. 
Line 59 pg 13 and line 5 bag 14 - FMT is not considered a probiotic preparation.
Please revised
It is stated that no serious adverse events occurred. Was diarrhea not considered
serious? Duration is important? The GSRS diarrhea syndrome would provide
insight here too. 
Minor edits
Pg 7 Line 17/18 delete "in a refrigerator" 
Separate the discussion of LHBT method and FMT in the discussion - separate
paragraphs. 
Table 1- would recommend 3 significant figures as 4 suggests too high of
precision
Table 2 - Revise to GSRS syndromes vs total scores. Choose this table or the
figure, not both 
Table 2 - Is this table Adverse events? Please delete. This information can just be
presented in the text. A section of text is misplaced below table 3. 
Fig 3. Recommend deletion of B frame as this is only a case study
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes