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  
 
Version: 0 Date: 17 Jun 2018  
 
Reviewer: Siobhain O'Mahony  
 
Reviewer's report:  
 
Linsalata et al., present a well written set of experiments. They inves tigate the permeability of 
the small intestine of diarrhoea predominant IBS patients in comparison to healthy controls and 
celiac patients. Levels of urinary sucrose, lactulose and mannitol were measured for 5 hours after 
consumption. They also investigate d circulating inflammatory factors in the blood. They divided 
the IBS group into those that had changes to small bowel permeability and those that did not -this 
was a good strategy but I couldn't find the graphs associated with the 2 IBS subgroups. This was  
a shame as the comparison of the IBS group as a whole looked very similar to the healthy 
controls. While the experiments were carried out very well as far as can be seen the findings 
presented are not that exciting in the current form.   
 
 
 
Comments:  
 
There are some English and grammatical errors the should be corrected.  
 
 
Both the introduction and discussion are greatly lacking the significance of changes in gut 
permeability -as in what are the functional consequences? Also there is very little 
mention/discus sion to the impact of stress and gut permeability -the addition of a questionnaire 
on perceived stress would have been useful to divide the groups also.  
 
 
Small versus large intestinal permeability should be discussed.  
 
 
Studies show that measuring the suga rs at one timepoint may not provide meaning full data -I 
would suggest the authors repeat the test and analyse samples collected at 30 minute intervals 
(where possible). How were the samples collected and where and when and how brought to the 
lab for analys is? Were samples frozen?  
 
 
Recruitment and screening of patients was very thorough but the authors state that this would 
obtain a homogenous group but clearly it is not a homogeneous group -this is fine but I would 
suggest "as homogeneous as possible".  
 
 
How was the phase of the female cycle confirmed and why was this phase chosen? The influence 
of hormones on gut permeability and differences between the genders with regard to IBS and 
celiac disease should be discussed.  
 
 
There are no justification for the statistics used and the section should be more descriptive.  
 
 
The significant symbols (a, b etc) on the graphs need to be described in the legends.  
 
 
 
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.  
 
No 
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate the qualit y 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, 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.  
 
none  
 
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  
 
Version: 0 Date: 17 Jun 2018  
 
Reviewer: Siobhain O'Mahony  
 
Reviewer's report:  
 
Linsalata et al., present a well written set of experiments. They inves tigate the permeability of 
the small intestine of diarrhoea predominant IBS patients in comparison to healthy controls and 
celiac patients. Levels of urinary sucrose, lactulose and mannitol were measured for 5 hours after 
consumption. They also investigate d circulating inflammatory factors in the blood. They divided 
the IBS group into those that had changes to small bowel permeability and those that did not -this 
was a good strategy but I couldn't find the graphs associated with the 2 IBS subgroups. This was  
a shame as the comparison of the IBS group as a whole looked very similar to the healthy 
controls. While the experiments were carried out very well as far as can be seen the findings 
presented are not that exciting in the current form.   
 
 
 
Comments:  
 
There are some English and grammatical errors the should be corrected.  
 
 
Both the introduction and discussion are greatly lacking the significance of changes in gut 
permeability -as in what are the functional consequences? Also there is very little 
mention/discus sion to the impact of stress and gut permeability -the addition of a questionnaire 
on perceived stress would have been useful to divide the groups also.  
 
 
Small versus large intestinal permeability should be discussed.  
 
 
Studies show that measuring the suga rs at one timepoint may not provide meaning full data -I 
would suggest the authors repeat the test and analyse samples collected at 30 minute intervals 
(where possible). How were the samples collected and where and when and how brought to the 
lab for analys is? Were samples frozen?  
 
 
Recruitment and screening of patients was very thorough but the authors state that this would 
obtain a homogenous group but clearly it is not a homogeneous group -this is fine but I would 
suggest "as homogeneous as possible".  
 
 
How was the phase of the female cycle confirmed and why was this phase chosen? The influence 
of hormones on gut permeability and differences between the genders with regard to IBS and 
celiac disease should be discussed.  
 
 
There are no justification for the statistics used and the section should be more descriptive.  
 
 
The significant symbols (a, b etc) on the graphs need to be described in the legends.  
 
 
 
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.  
 
No 
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate the qualit y 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, 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.  
 
none  
 
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  
 
Version: 0 Date: 17 Jun 2018  
 
Reviewer: Siobhain O'Mahony  
 
Reviewer's report:  
 
Linsalata et al., present a well written set of experiments. They inves tigate the permeability of 
the small intestine of diarrhoea predominant IBS patients in comparison to healthy controls and 
celiac patients. Levels of urinary sucrose, lactulose and mannitol were measured for 5 hours after 
consumption. They also investigate d circulating inflammatory factors in the blood. They divided 
the IBS group into those that had changes to small bowel permeability and those that did not -this 
was a good strategy but I couldn't find the graphs associated with the 2 IBS subgroups. This was  
a shame as the comparison of the IBS group as a whole looked very similar to the healthy 
controls. While the experiments were carried out very well as far as can be seen the findings 
presented are not that exciting in the current form.   
 
 
 
Comments:  
 
There are some English and grammatical errors the should be corrected.  
 
 
Both the introduction and discussion are greatly lacking the significance of changes in gut 
permeability -as in what are the functional consequences? Also there is very little 
mention/discus sion to the impact of stress and gut permeability -the addition of a questionnaire 
on perceived stress would have been useful to divide the groups also.  
 
 
Small versus large intestinal permeability should be discussed.  
 
 
Studies show that measuring the suga rs at one timepoint may not provide meaning full data -I 
would suggest the authors repeat the test and analyse samples collected at 30 minute intervals 
(where possible). How were the samples collected and where and when and how brought to the 
lab for analys is? Were samples frozen?  
 
 
Recruitment and screening of patients was very thorough but the authors state that this would 
obtain a homogenous group but clearly it is not a homogeneous group -this is fine but I would 
suggest "as homogeneous as possible".  
 
 
How was the phase of the female cycle confirmed and why was this phase chosen? The influence 
of hormones on gut permeability and differences between the genders with regard to IBS and 
celiac disease should be discussed.  
 
 
There are no justification for the statistics used and the section should be more descriptive.  
 
 
The significant symbols (a, b etc) on the graphs need to be described in the legends.  
 
 
 
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.  
 
No 
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate the qualit y 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, 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.  
 
none  
 
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