Reviewer ’s report  
 
Title: Fecal microbiota composition is linked to the postoperative disease course in patients with  
Crohn’s disease  
 
Version: 0 Date: 04 Feb 2020  
 
Reviewer: Kerri Glassner  
 
Reviewer's report:  
 
Strombeck et al investigated the association of the fecal microbiota composition (determined by 
a high throughput test quantifyin g a pre -selected set of bacteria) with the postoperative disease 
status of CD patients. There is considerable interest in the role of the microbiome in post -
operative disease recurrence. Clinicians are in need of better ways to predict which CD patients 
are at high risk of disease recurrence and necessitate early biologic therapy postoperatively.  The 
current study is of considerable interest as it involves the use of a GA -map dysbiosis test which 
targets &gt;300 bacteria on different taxonomic levels thus simplifying the analysis. The authors 
found that at one year after ileocolonic resection, the fecal microbiota composition differentiated 
CD patients from healthy subjects, and could be used to separate CD patients in endoscopic 
remission and with endoscop ic disease recurrence. In addition, the fecal microbiota composition 
at early follow up after surgery was similar to one year follow up suggesting little variation 
during the first year after surgery.  
 
The findings of the study are very interesting at a t ime where we continue to look for 
noninvasive biomarkers to help predict disease course in IBD. However, there are few points that 
need to be addressed.  
 
1. The study enrolled only a small number of patients with 21 CD and 7 healthy controls. In 
addition,  only 8 patients provided samples at early follow up. This is a significant limitation and 
limits generalizability.  
 
2. All patients were on antibiotics for post -operative prophylaxis. When were the antibiotics 
started postoperatively? How long were they continued? Were the patients who had early stool 
testing already on antibiotics?  
 
3. Exclusion criteria include disease activity beyond the ileocecal region, however Table 1 lists 5 
patients with penetrating disease. Was the penetrating disease only in th e ileocecal region? Was 
this removed during surgery? Or was this a history of penetrating disease in the past?  
 
4. There were 3 present smokers. Did smoking have any impact on microbial composition or 
disease recurrence?  
 
5. Patients were on varying medi cations both at the time of the resection and at the time of the 
colonoscopy. When was medical therapy started post -operatively? In the 8 who had the early 
stool sample collected were they already on medical therapy? If the aim of the study was to 
predict those at high risk for disease recurrence it seems that the patients should have been off of 
medical therapy or at least on the same therapy. Were those on medical therapy less likely to 
have recurrence and was there any association with medical therapy an d the microbiota changes?  
 
6. What was the reason for the surgery? Purely fibrostenotic disease? Did all patients have active 
inflammation? If some patients had active inflammatory disease and some had only fibrostenotic 
disease this may have impacted the  outcomes.  
 
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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.  
 
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 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: 04 Feb 2020  
 
Reviewer: Kerri Glassner  
 
Reviewer's report:  
 
Strombeck et al investigated the association of the fecal microbiota composition (determined by 
a high throughput test quantifyin g a pre -selected set of bacteria) with the postoperative disease 
status of CD patients. There is considerable interest in the role of the microbiome in post -
operative disease recurrence. Clinicians are in need of better ways to predict which CD patients 
are at high risk of disease recurrence and necessitate early biologic therapy postoperatively.  The 
current study is of considerable interest as it involves the use of a GA -map dysbiosis test which 
targets &gt;300 bacteria on different taxonomic levels thus simplifying the analysis. The authors 
found that at one year after ileocolonic resection, the fecal microbiota composition differentiated 
CD patients from healthy subjects, and could be used to separate CD patients in endoscopic 
remission and with endoscop ic disease recurrence. In addition, the fecal microbiota composition 
at early follow up after surgery was similar to one year follow up suggesting little variation 
during the first year after surgery.  
 
The findings of the study are very interesting at a t ime where we continue to look for 
noninvasive biomarkers to help predict disease course in IBD. However, there are few points that 
need to be addressed.  
 
1. The study enrolled only a small number of patients with 21 CD and 7 healthy controls. In 
addition,  only 8 patients provided samples at early follow up. This is a significant limitation and 
limits generalizability.  
 
2. All patients were on antibiotics for post -operative prophylaxis. When were the antibiotics 
started postoperatively? How long were they continued? Were the patients who had early stool 
testing already on antibiotics?  
 
3. Exclusion criteria include disease activity beyond the ileocecal region, however Table 1 lists 5 
patients with penetrating disease. Was the penetrating disease only in th e ileocecal region? Was 
this removed during surgery? Or was this a history of penetrating disease in the past?  
 
4. There were 3 present smokers. Did smoking have any impact on microbial composition or 
disease recurrence?  
 
5. Patients were on varying medi cations both at the time of the resection and at the time of the 
colonoscopy. When was medical therapy started post -operatively? In the 8 who had the early 
stool sample collected were they already on medical therapy? If the aim of the study was to 
predict those at high risk for disease recurrence it seems that the patients should have been off of 
medical therapy or at least on the same therapy. Were those on medical therapy less likely to 
have recurrence and was there any association with medical therapy an d the microbiota changes?  
 
6. What was the reason for the surgery? Purely fibrostenotic disease? Did all patients have active 
inflammation? If some patients had active inflammatory disease and some had only fibrostenotic 
disease this may have impacted the  outcomes.  
 
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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.  
 
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 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: 04 Feb 2020  
 
Reviewer: Kerri Glassner  
 
Reviewer's report:  
 
Strombeck et al investigated the association of the fecal microbiota composition (determined by 
a high throughput test quantifyin g a pre -selected set of bacteria) with the postoperative disease 
status of CD patients. There is considerable interest in the role of the microbiome in post -
operative disease recurrence. Clinicians are in need of better ways to predict which CD patients 
are at high risk of disease recurrence and necessitate early biologic therapy postoperatively.  The 
current study is of considerable interest as it involves the use of a GA -map dysbiosis test which 
targets &gt;300 bacteria on different taxonomic levels thus simplifying the analysis. The authors 
found that at one year after ileocolonic resection, the fecal microbiota composition differentiated 
CD patients from healthy subjects, and could be used to separate CD patients in endoscopic 
remission and with endoscop ic disease recurrence. In addition, the fecal microbiota composition 
at early follow up after surgery was similar to one year follow up suggesting little variation 
during the first year after surgery.  
 
The findings of the study are very interesting at a t ime where we continue to look for 
noninvasive biomarkers to help predict disease course in IBD. However, there are few points that 
need to be addressed.  
 
1. The study enrolled only a small number of patients with 21 CD and 7 healthy controls. In 
addition,  only 8 patients provided samples at early follow up. This is a significant limitation and 
limits generalizability.  
 
2. All patients were on antibiotics for post -operative prophylaxis. When were the antibiotics 
started postoperatively? How long were they continued? Were the patients who had early stool 
testing already on antibiotics?  
 
3. Exclusion criteria include disease activity beyond the ileocecal region, however Table 1 lists 5 
patients with penetrating disease. Was the penetrating disease only in th e ileocecal region? Was 
this removed during surgery? Or was this a history of penetrating disease in the past?  
 
4. There were 3 present smokers. Did smoking have any impact on microbial composition or 
disease recurrence?  
 
5. Patients were on varying medi cations both at the time of the resection and at the time of the 
colonoscopy. When was medical therapy started post -operatively? In the 8 who had the early 
stool sample collected were they already on medical therapy? If the aim of the study was to 
predict those at high risk for disease recurrence it seems that the patients should have been off of 
medical therapy or at least on the same therapy. Were those on medical therapy less likely to 
have recurrence and was there any association with medical therapy an d the microbiota changes?  
 
6. What was the reason for the surgery? Purely fibrostenotic disease? Did all patients have active 
inflammation? If some patients had active inflammatory disease and some had only fibrostenotic 
disease this may have impacted the  outcomes.  
 
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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.  
 
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 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