Reviewer ’s report  
 
Title: Fecal microbiota composition is linked to the postoperative disease course in patients with  
Crohn’s disease  
 
Version: 0 Date: 01 Feb 2020  
 
Reviewer: Faming Zhang  
 
Reviewer's report:  
 
Comments to Author:  
This paper evaluated whether the fecal microbiota composition,  determined by a high throughput 
test quantifying a pre -selected set of bacteria, is associated with the postoperative disease course 
of CD patients. The results indicated the fecal microbiota composition of CD patients analyzed 
by GA -map Dysbiosis test ma y potentially be used as a non -invasive diagnostic tool for the 
postoperative disease course. This is a very interesting topic and worth of investigation. 
However, it reserves some problems.    
REQUESTED REVISIONS:  
1. Line 7 -8, page 4. The authors proposed  that approximately 50% of adult patients with 
CD are in need of surgery within 10 years of diagnosis. But the cited references (Biroulet et al., 
2010; Ramadas et al., 2010) were not the latest research results. In the introduction section, the 
references published in the last three years should be more cited.  
2. Line 32 -33, page 4. Agree that the gut microbial profiles between patients with CD and 
healthy individuals were different. The following papers recently published should be discussed 
in the manusc ript: 
1) Glassner KL, Abraham BP, Quigley EMM (2020). The microbiome and inflammatory 
bowel disease. J. Allergy Clin. Immunol. 2020 Jan;145(1).  
2) Pittayanon R,  Lau JT,  Leontiadis GI,  Tse F,  Yuan Y,  Surette M,  Moayyedi P 
(2019). Differences in Gut Microbiota in Patients With vs Without Inflammatory Bowel 
Diseases: a Systematic Review. Gastroenterology 2019 Dec 05.  
3) Wang H, Cui B, Li Q, Ding X, Li P, Zhang T, Yang X, Ji G, Zhang F (2018). The 
safety of fecal mi crobiota transplantation for Crohn's disease: findings from a long -term study. 
Adv Ther 35:1935 -1944.  
4) Li P, Zhang T, Xiao Y, Tian L, Cui B, Ji G, Liu YY, Zhang F. Timing for the second 
fecal microbiota transplantation to maintain the long -term benefit f rom the first treatment for 
Crohn's disease. Appl Microbiol Biotechnol 2019; 103:349 -360. 
3. Line 5 -6, page 6. This is a prospective or a retrospective study? For the inclusion 
criteria, the patients' age was defined as 17 -63 years. How is this age range d etermined?  
4. The authors declared that all patients were given perioperative antibiotic prophylaxis. 
The use of antibiotics was considered to have a great effect on the composition of gut 
microbiota. However, the authors did not collect stool samples bef ore and after antibiotic use, as 
well as before surgery to assess this impact. Please clarify this problem.  
5. Line 46 -47, Line 54 -55, page 6. Why some fecal samples were stored at -20°C, and 
others were stored at -80°C?  
6. Table 3. The sample size is smal l, and it should be a limitation to the conclusion. From 
this table, the microbiota cluster was found to be associated with post -operative status. However, 
further ROC curves should be given to determine whether fecal microbiota composition could be 
used a s a non -invasive diagnostic tool.  
7. Need for extensive English editing.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comme nts 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 c omments 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 am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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 publi cation 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 curr ently 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.  
 
None.  
 
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 w ill 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: Fecal microbiota composition is linked to the postoperative disease course in patients with  
Crohn’s disease  
 
Version: 0 Date: 01 Feb 2020  
 
Reviewer: Faming Zhang  
 
Reviewer's report:  
 
Comments to Author:  
This paper evaluated whether the fecal microbiota composition,  determined by a high throughput 
test quantifying a pre -selected set of bacteria, is associated with the postoperative disease course 
of CD patients. The results indicated the fecal microbiota composition of CD patients analyzed 
by GA -map Dysbiosis test ma y potentially be used as a non -invasive diagnostic tool for the 
postoperative disease course. This is a very interesting topic and worth of investigation. 
However, it reserves some problems.    
REQUESTED REVISIONS:  
1. Line 7 -8, page 4. The authors proposed  that approximately 50% of adult patients with 
CD are in need of surgery within 10 years of diagnosis. But the cited references (Biroulet et al., 
2010; Ramadas et al., 2010) were not the latest research results. In the introduction section, the 
references published in the last three years should be more cited.  
2. Line 32 -33, page 4. Agree that the gut microbial profiles between patients with CD and 
healthy individuals were different. The following papers recently published should be discussed 
in the manusc ript: 
1) Glassner KL, Abraham BP, Quigley EMM (2020). The microbiome and inflammatory 
bowel disease. J. Allergy Clin. Immunol. 2020 Jan;145(1).  
2) Pittayanon R,  Lau JT,  Leontiadis GI,  Tse F,  Yuan Y,  Surette M,  Moayyedi P 
(2019). Differences in Gut Microbiota in Patients With vs Without Inflammatory Bowel 
Diseases: a Systematic Review. Gastroenterology 2019 Dec 05.  
3) Wang H, Cui B, Li Q, Ding X, Li P, Zhang T, Yang X, Ji G, Zhang F (2018). The 
safety of fecal mi crobiota transplantation for Crohn's disease: findings from a long -term study. 
Adv Ther 35:1935 -1944.  
4) Li P, Zhang T, Xiao Y, Tian L, Cui B, Ji G, Liu YY, Zhang F. Timing for the second 
fecal microbiota transplantation to maintain the long -term benefit f rom the first treatment for 
Crohn's disease. Appl Microbiol Biotechnol 2019; 103:349 -360. 
3. Line 5 -6, page 6. This is a prospective or a retrospective study? For the inclusion 
criteria, the patients' age was defined as 17 -63 years. How is this age range d etermined?  
4. The authors declared that all patients were given perioperative antibiotic prophylaxis. 
The use of antibiotics was considered to have a great effect on the composition of gut 
microbiota. However, the authors did not collect stool samples bef ore and after antibiotic use, as 
well as before surgery to assess this impact. Please clarify this problem.  
5. Line 46 -47, Line 54 -55, page 6. Why some fecal samples were stored at -20°C, and 
others were stored at -80°C?  
6. Table 3. The sample size is smal l, and it should be a limitation to the conclusion. From 
this table, the microbiota cluster was found to be associated with post -operative status. However, 
further ROC curves should be given to determine whether fecal microbiota composition could be 
used a s a non -invasive diagnostic tool.  
7. Need for extensive English editing.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comme nts 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 c omments 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 am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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 publi cation 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 curr ently 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.  
 
None.  
 
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 w ill 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: Fecal microbiota composition is linked to the postoperative disease course in patients with  
Crohn’s disease  
 
Version: 0 Date: 01 Feb 2020  
 
Reviewer: Faming Zhang  
 
Reviewer's report:  
 
Comments to Author:  
This paper evaluated whether the fecal microbiota composition,  determined by a high throughput 
test quantifying a pre -selected set of bacteria, is associated with the postoperative disease course 
of CD patients. The results indicated the fecal microbiota composition of CD patients analyzed 
by GA -map Dysbiosis test ma y potentially be used as a non -invasive diagnostic tool for the 
postoperative disease course. This is a very interesting topic and worth of investigation. 
However, it reserves some problems.    
REQUESTED REVISIONS:  
1. Line 7 -8, page 4. The authors proposed  that approximately 50% of adult patients with 
CD are in need of surgery within 10 years of diagnosis. But the cited references (Biroulet et al., 
2010; Ramadas et al., 2010) were not the latest research results. In the introduction section, the 
references published in the last three years should be more cited.  
2. Line 32 -33, page 4. Agree that the gut microbial profiles between patients with CD and 
healthy individuals were different. The following papers recently published should be discussed 
in the manusc ript: 
1) Glassner KL, Abraham BP, Quigley EMM (2020). The microbiome and inflammatory 
bowel disease. J. Allergy Clin. Immunol. 2020 Jan;145(1).  
2) Pittayanon R,  Lau JT,  Leontiadis GI,  Tse F,  Yuan Y,  Surette M,  Moayyedi P 
(2019). Differences in Gut Microbiota in Patients With vs Without Inflammatory Bowel 
Diseases: a Systematic Review. Gastroenterology 2019 Dec 05.  
3) Wang H, Cui B, Li Q, Ding X, Li P, Zhang T, Yang X, Ji G, Zhang F (2018). The 
safety of fecal mi crobiota transplantation for Crohn's disease: findings from a long -term study. 
Adv Ther 35:1935 -1944.  
4) Li P, Zhang T, Xiao Y, Tian L, Cui B, Ji G, Liu YY, Zhang F. Timing for the second 
fecal microbiota transplantation to maintain the long -term benefit f rom the first treatment for 
Crohn's disease. Appl Microbiol Biotechnol 2019; 103:349 -360. 
3. Line 5 -6, page 6. This is a prospective or a retrospective study? For the inclusion 
criteria, the patients' age was defined as 17 -63 years. How is this age range d etermined?  
4. The authors declared that all patients were given perioperative antibiotic prophylaxis. 
The use of antibiotics was considered to have a great effect on the composition of gut 
microbiota. However, the authors did not collect stool samples bef ore and after antibiotic use, as 
well as before surgery to assess this impact. Please clarify this problem.  
5. Line 46 -47, Line 54 -55, page 6. Why some fecal samples were stored at -20°C, and 
others were stored at -80°C?  
6. Table 3. The sample size is smal l, and it should be a limitation to the conclusion. From 
this table, the microbiota cluster was found to be associated with post -operative status. However, 
further ROC curves should be given to determine whether fecal microbiota composition could be 
used a s a non -invasive diagnostic tool.  
7. Need for extensive English editing.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comme nts 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 c omments 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 am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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 publi cation 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 curr ently 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.  
 
None.  
 
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 w ill 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