Reviewer’s report
Title: 
Non-Celiac Wheat Sensitivity: Rationality and Irrationality of a Gluten-
Free Diet in Individuals affected with Non-Celiac Disease
Version: 
0 
Date: 
16 Apr 2020
Reviewer's report:
In this comprehensive review, the Authors present and discuss current evidence
and personal experience about non-Celiac gluten/wheat sensitivity. It is an
interesting, up-to-date narrative review. I appreciated the emphasis on evidence
but with information about the experience of the experts. 
Major comments: 
1. Most of the Randomized clinical trials cited in Table 1 are not cited in the
Bibliography. All mentioned studies should be correctly cited and appear in the
Bibliography. 
2. I think that two topics should be addressed, considering the controversial data
on minor duodenal mucosal lesions in the setting of non-celiac gluten/wheat
sensitivity: 
a. the IEL count in the Marsh classification has been validated in H&E staining,
while I am told that no clear cut off for IELs in healthy/inflamed/celiac subjects
have been yet validated with the CD3 staining. Yet many pathologists (in my
experience) use the CD3 Staining to evaluate the presence of increased IELs.
This could lead to overestimation of the cases with nearly increased or slightly
increased IELs, which plays a role in the complex field of non-celiac
gluten/wheat sensitivity). I think it is necessary to clarify this point, both
including literature data if available and the personal experience of the
Pathologist.
b. Similarly, the role of Helicobacter pylori in this context (differential diagnosis
of dyspepsia/abdominal discomfort in patients with suspected NCG/W-S +
possible cause for duodenal inflammation and increased IELs) should be
mentioned/discussed
Minor comments:
1. The "main text" starts abruptly, as if it were in continuity with the
background. I suggest reformulating 
in order to mark logically the passage
between background and main text.
2. Line 118 "In a world where social media are propagating facts with fake
news": I understand the concept but the phrase is ambiguous, please reformulate.
3. Line 167-168 "One of the problems is that it continues to struggle
gastroenterologists and pathologists is the heterogeneity of some population",
please correct.
4. Line 199-200 "The taxonomy in gastroenterology is much more complicated
than in sciences like botanic": unnecessary and non necessarily correct
comment/comparison, I find it not compatible with the high scientific level of
the paper 
5. Line 215-216: "Of course, there are clear-cut cases of celiac disease, but few
cases of IELs may easily cross the borders of the categories." Unclear, please
reformulate
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 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 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 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 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 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: 
Non-Celiac Wheat Sensitivity: Rationality and Irrationality of a Gluten-
Free Diet in Individuals affected with Non-Celiac Disease
Version: 
0 
Date: 
16 Apr 2020
Reviewer's report:
In this comprehensive review, the Authors present and discuss current evidence
and personal experience about non-Celiac gluten/wheat sensitivity. It is an
interesting, up-to-date narrative review. I appreciated the emphasis on evidence
but with information about the experience of the experts. 
Major comments: 
1. Most of the Randomized clinical trials cited in Table 1 are not cited in the
Bibliography. All mentioned studies should be correctly cited and appear in the
Bibliography. 
2. I think that two topics should be addressed, considering the controversial data
on minor duodenal mucosal lesions in the setting of non-celiac gluten/wheat
sensitivity: 
a. the IEL count in the Marsh classification has been validated in H&E staining,
while I am told that no clear cut off for IELs in healthy/inflamed/celiac subjects
have been yet validated with the CD3 staining. Yet many pathologists (in my
experience) use the CD3 Staining to evaluate the presence of increased IELs.
This could lead to overestimation of the cases with nearly increased or slightly
increased IELs, which plays a role in the complex field of non-celiac
gluten/wheat sensitivity). I think it is necessary to clarify this point, both
including literature data if available and the personal experience of the
Pathologist.
b. Similarly, the role of Helicobacter pylori in this context (differential diagnosis
of dyspepsia/abdominal discomfort in patients with suspected NCG/W-S +
possible cause for duodenal inflammation and increased IELs) should be
mentioned/discussed
Minor comments:
1. The "main text" starts abruptly, as if it were in continuity with the
background. I suggest reformulating 
in order to mark logically the passage
between background and main text.
2. Line 118 "In a world where social media are propagating facts with fake
news": I understand the concept but the phrase is ambiguous, please reformulate.
3. Line 167-168 "One of the problems is that it continues to struggle
gastroenterologists and pathologists is the heterogeneity of some population",
please correct.
4. Line 199-200 "The taxonomy in gastroenterology is much more complicated
than in sciences like botanic": unnecessary and non necessarily correct
comment/comparison, I find it not compatible with the high scientific level of
the paper 
5. Line 215-216: "Of course, there are clear-cut cases of celiac disease, but few
cases of IELs may easily cross the borders of the categories." Unclear, please
reformulate
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 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 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 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 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 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: 
Non-Celiac Wheat Sensitivity: Rationality and Irrationality of a Gluten-
Free Diet in Individuals affected with Non-Celiac Disease
Version: 
0 
Date: 
16 Apr 2020
Reviewer's report:
In this comprehensive review, the Authors present and discuss current evidence
and personal experience about non-Celiac gluten/wheat sensitivity. It is an
interesting, up-to-date narrative review. I appreciated the emphasis on evidence
but with information about the experience of the experts. 
Major comments: 
1. Most of the Randomized clinical trials cited in Table 1 are not cited in the
Bibliography. All mentioned studies should be correctly cited and appear in the
Bibliography. 
2. I think that two topics should be addressed, considering the controversial data
on minor duodenal mucosal lesions in the setting of non-celiac gluten/wheat
sensitivity: 
a. the IEL count in the Marsh classification has been validated in H&E staining,
while I am told that no clear cut off for IELs in healthy/inflamed/celiac subjects
have been yet validated with the CD3 staining. Yet many pathologists (in my
experience) use the CD3 Staining to evaluate the presence of increased IELs.
This could lead to overestimation of the cases with nearly increased or slightly
increased IELs, which plays a role in the complex field of non-celiac
gluten/wheat sensitivity). I think it is necessary to clarify this point, both
including literature data if available and the personal experience of the
Pathologist.
b. Similarly, the role of Helicobacter pylori in this context (differential diagnosis
of dyspepsia/abdominal discomfort in patients with suspected NCG/W-S +
possible cause for duodenal inflammation and increased IELs) should be
mentioned/discussed
Minor comments:
1. The "main text" starts abruptly, as if it were in continuity with the
background. I suggest reformulating 
in order to mark logically the passage
between background and main text.
2. Line 118 "In a world where social media are propagating facts with fake
news": I understand the concept but the phrase is ambiguous, please reformulate.
3. Line 167-168 "One of the problems is that it continues to struggle
gastroenterologists and pathologists is the heterogeneity of some population",
please correct.
4. Line 199-200 "The taxonomy in gastroenterology is much more complicated
than in sciences like botanic": unnecessary and non necessarily correct
comment/comparison, I find it not compatible with the high scientific level of
the paper 
5. Line 215-216: "Of course, there are clear-cut cases of celiac disease, but few
cases of IELs may easily cross the borders of the categories." Unclear, please
reformulate
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 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 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 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 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 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