Reviewer ’s report  
 
Title:  Faecal microbiota transplantation: a regulatory hurdle?  
 
Version: 0 Date: 21 May 2017 
 
Reviewer:  Christoph  Högenauer  
 
Reviewer’s report:  
 
This paper describes the uncertainties in regulatory issues for fecal microbiota transplantation. 
The authors suggest to contr ol FMT by the gene -, cell - tissue regulations of the European Union.  
 
I believe the topic of the paper is of significant interest for the community of gastroenterologists.  
In general the paper is well written and the issues regarding this open question are  addressed 
adequately.  
 
 
I have some comments:  
 
Paragraph on "Faecal microbiota transplantation: viewpoint regulatory authorities": It should be 
specifically mentioned that for most European counties there is no regulation on FMT at all.  
 
Paragraph on "A p ragmatic regulatory approach for a quickly evolving therapy": As most readers 
of this article will be not familiar with the gene -, cell - tissue regulations of the European Union, I 
would suggest to explain the according regulations in more details and how it would affect 
clinical practice. How would this regulation apply if a patient is treated for recurrent CDI by 
FMT in clinical practice? Is this the same process as for blood transfusions in clinical practice?  
How would this regulation apply for clinical  studies on FMT for other indications? Which 
authority is responsible? How does the application process work in practice?  
 
 
Minor comments:  
 
Page 4, line 38: "Unfortunately, a considerable number of patients will suffer relapse 3 months 
post treatment" I be lieve the authors mean up to 3 months.  
 
Page 4, line 40: "Faecal microbiota transplantation (FMT), as a last therapeutic option, consists 
of the administration of a stool sample from a healthy donor to the patient, hence transferring the 
donor's microbiome "   I am not sure if a stool sample is the correct word. Usually 50 to 100g of 
stool is used for FMT, this is not a sample.  
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
Qualit y 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 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 w ay 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 sal ary 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 have received a research gr ant from Seres Therapeutics Inc  
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 websi te 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:  Faecal microbiota transplantation: a regulatory hurdle?  
 
Version: 0 Date: 21 May 2017 
 
Reviewer:  Christoph  Högenauer  
 
Reviewer’s report:  
 
This paper describes the uncertainties in regulatory issues for fecal microbiota transplantation. 
The authors suggest to contr ol FMT by the gene -, cell - tissue regulations of the European Union.  
 
I believe the topic of the paper is of significant interest for the community of gastroenterologists.  
In general the paper is well written and the issues regarding this open question are  addressed 
adequately.  
 
 
I have some comments:  
 
Paragraph on "Faecal microbiota transplantation: viewpoint regulatory authorities": It should be 
specifically mentioned that for most European counties there is no regulation on FMT at all.  
 
Paragraph on "A p ragmatic regulatory approach for a quickly evolving therapy": As most readers 
of this article will be not familiar with the gene -, cell - tissue regulations of the European Union, I 
would suggest to explain the according regulations in more details and how it would affect 
clinical practice. How would this regulation apply if a patient is treated for recurrent CDI by 
FMT in clinical practice? Is this the same process as for blood transfusions in clinical practice?  
How would this regulation apply for clinical  studies on FMT for other indications? Which 
authority is responsible? How does the application process work in practice?  
 
 
Minor comments:  
 
Page 4, line 38: "Unfortunately, a considerable number of patients will suffer relapse 3 months 
post treatment" I be lieve the authors mean up to 3 months.  
 
Page 4, line 40: "Faecal microbiota transplantation (FMT), as a last therapeutic option, consists 
of the administration of a stool sample from a healthy donor to the patient, hence transferring the 
donor's microbiome "   I am not sure if a stool sample is the correct word. Usually 50 to 100g of 
stool is used for FMT, this is not a sample.  
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
Qualit y 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 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 w ay 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 sal ary 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 have received a research gr ant from Seres Therapeutics Inc  
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 websi te 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:  Faecal microbiota transplantation: a regulatory hurdle?  
 
Version: 0 Date: 21 May 2017 
 
Reviewer:  Christoph  Högenauer  
 
Reviewer’s report:  
 
This paper describes the uncertainties in regulatory issues for fecal microbiota transplantation. 
The authors suggest to contr ol FMT by the gene -, cell - tissue regulations of the European Union.  
 
I believe the topic of the paper is of significant interest for the community of gastroenterologists.  
In general the paper is well written and the issues regarding this open question are  addressed 
adequately.  
 
 
I have some comments:  
 
Paragraph on "Faecal microbiota transplantation: viewpoint regulatory authorities": It should be 
specifically mentioned that for most European counties there is no regulation on FMT at all.  
 
Paragraph on "A p ragmatic regulatory approach for a quickly evolving therapy": As most readers 
of this article will be not familiar with the gene -, cell - tissue regulations of the European Union, I 
would suggest to explain the according regulations in more details and how it would affect 
clinical practice. How would this regulation apply if a patient is treated for recurrent CDI by 
FMT in clinical practice? Is this the same process as for blood transfusions in clinical practice?  
How would this regulation apply for clinical  studies on FMT for other indications? Which 
authority is responsible? How does the application process work in practice?  
 
 
Minor comments:  
 
Page 4, line 38: "Unfortunately, a considerable number of patients will suffer relapse 3 months 
post treatment" I be lieve the authors mean up to 3 months.  
 
Page 4, line 40: "Faecal microbiota transplantation (FMT), as a last therapeutic option, consists 
of the administration of a stool sample from a healthy donor to the patient, hence transferring the 
donor's microbiome "   I am not sure if a stool sample is the correct word. Usually 50 to 100g of 
stool is used for FMT, this is not a sample.  
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
Qualit y 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 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 w ay 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 sal ary 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 have received a research gr ant from Seres Therapeutics Inc  
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 websi te 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