Reviewer ’s report  
 
Title: NONINVASIVE BIOMARKERS OF GU T BARRIER FUNCTION IDENTIFY TWO 
SUBTYPES OF PATIENTS SUFFERING FR OM DIARRHOEA PREDOMINANT -IBS: A 
CASE -CONTROL STUDY  
 
Versio n: 0 Date: 13 Jul 2018  
 
Reviewer: Massimo Bellini  
 
Reviewer's report:  
 
It is a paper dealing with a very interesting matter.  
 
The aim of the study is clearly defined and the methods are well described  
 
The data are easily understandable and the discussion and conclusions are well b alanced and 
adequately supported by the data.  
 
Limitations of the work are clearly stated  
 
 
 
Comments  
 
- Did the authors consider the alteration of any protein of  the "Claudine family"? There are 
at least 24 different claudines and some of them (e.g. Claudine 1) could be involved in  
the mucosal barrier changes…  
 
 
- In order to better verify  the hypothesis  o f a low grade inflammation it would have  been 
very interesting performing biopsies of duodenum and colon during gastroscopy and 
colonoscopy.  
 
 
- A comment about  the  51Cr -EDTA for  assessing the intestinal permeability and its 
possible use as an a alternati ve to HPLC urinary assessment of sugars excretion  would 
be welcome  
 
 
Minor changes  
 
Pag 14:".. D -IBS and CD patients were not different in their synmptomatology": the authors 
should precise that thei statement is referred only to bowel habits and abdominal symptoms.  
 
 
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 yo ur comments to the authors.  
 
Yes 
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 qualit y 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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 receiv ed 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will 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 m y named report can be in cluded as confidential comments 
to the editor s, which will not be pub lished.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: NONINVASIVE BIOMARKERS OF GU T BARRIER FUNCTION IDENTIFY TWO 
SUBTYPES OF PATIENTS SUFFERING FR OM DIARRHOEA PREDOMINANT -IBS: A 
CASE -CONTROL STUDY  
 
Versio n: 0 Date: 13 Jul 2018  
 
Reviewer: Massimo Bellini  
 
Reviewer's report:  
 
It is a paper dealing with a very interesting matter.  
 
The aim of the study is clearly defined and the methods are well described  
 
The data are easily understandable and the discussion and conclusions are well b alanced and 
adequately supported by the data.  
 
Limitations of the work are clearly stated  
 
 
 
Comments  
 
- Did the authors consider the alteration of any protein of  the "Claudine family"? There are 
at least 24 different claudines and some of them (e.g. Claudine 1) could be involved in  
the mucosal barrier changes…  
 
 
- In order to better verify  the hypothesis  o f a low grade inflammation it would have  been 
very interesting performing biopsies of duodenum and colon during gastroscopy and 
colonoscopy.  
 
 
- A comment about  the  51Cr -EDTA for  assessing the intestinal permeability and its 
possible use as an a alternati ve to HPLC urinary assessment of sugars excretion  would 
be welcome  
 
 
Minor changes  
 
Pag 14:".. D -IBS and CD patients were not different in their synmptomatology": the authors 
should precise that thei statement is referred only to bowel habits and abdominal symptoms.  
 
 
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 yo ur comments to the authors.  
 
Yes 
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 qualit y 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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 receiv ed 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will 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 m y named report can be in cluded as confidential comments 
to the editor s, which will not be pub lished.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: NONINVASIVE BIOMARKERS OF GU T BARRIER FUNCTION IDENTIFY TWO 
SUBTYPES OF PATIENTS SUFFERING FR OM DIARRHOEA PREDOMINANT -IBS: A 
CASE -CONTROL STUDY  
 
Versio n: 0 Date: 13 Jul 2018  
 
Reviewer: Massimo Bellini  
 
Reviewer's report:  
 
It is a paper dealing with a very interesting matter.  
 
The aim of the study is clearly defined and the methods are well described  
 
The data are easily understandable and the discussion and conclusions are well b alanced and 
adequately supported by the data.  
 
Limitations of the work are clearly stated  
 
 
 
Comments  
 
- Did the authors consider the alteration of any protein of  the "Claudine family"? There are 
at least 24 different claudines and some of them (e.g. Claudine 1) could be involved in  
the mucosal barrier changes…  
 
 
- In order to better verify  the hypothesis  o f a low grade inflammation it would have  been 
very interesting performing biopsies of duodenum and colon during gastroscopy and 
colonoscopy.  
 
 
- A comment about  the  51Cr -EDTA for  assessing the intestinal permeability and its 
possible use as an a alternati ve to HPLC urinary assessment of sugars excretion  would 
be welcome  
 
 
Minor changes  
 
Pag 14:".. D -IBS and CD patients were not different in their synmptomatology": the authors 
should precise that thei statement is referred only to bowel habits and abdominal symptoms.  
 
 
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 yo ur comments to the authors.  
 
Yes 
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 qualit y 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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 receiv ed 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will 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 m y named report can be in cluded as confidential comments 
to the editor s, which will not be pub lished.  
 
I agree to the open peer review policy of the journal  
assistant