Reviewer’s report
Title: 
Non-Celiac Wheat Sensitivity: Rationality and Irrationality of a Gluten-
Free Diet in Individuals affected with Non-Celiac Disease
Version: 
1 
Date: 
28 Jun 2020
Reviewer's report:
I appreciated some of the changes to the Manuscript in order to clarify some
aspects and improve readability. 
However, there still are some issues that need to be addressed:
1. The term "gluten sensitive enteropathy" should not be used instead of celiac
disease (as suggested by the Oslo consensus on celiac disease terminology), it
confounds the reader adding yet another term, especially in a review focused on
the specificity of non-celiac gluten sensitivity. Later in the text other
confounding expressions such as "a non-GSE celiac symptomatologic pattern"
(Page 4 line 88-89) are used. I strongly suggest to use 
of the term "celiac
disease" only. 
Section Background: 
1. it is a shortened a easier to read introduction, but it starts with celiac disease
and its peculiarities and not with non-celiac gluten sensitivity, thus puzzling the
reader a bit. I suggest to start directly with the topic of the review itself. 
2. The following sentences are not quite clear and unnecessary lengthy (if the
aim is to express the concept that there are patients with suggestive symptoms
who don't have celiac disease):
"However, several patients may present with the symptomatology of the celiac
disease. Still, both biochemical values of anti-tissue transglutaminase antibodies
(ATTG), as well as duodenal histology, are probably unremarkable at first
glance. Confronted with this situation and struggling with the patients'
complaints, the gastroenterologist tries to have refuge in further diagnostic tests
or more complicated levels of genetic diagnosis.". 
Section Main text: 
1. The main text abruptly starts with the Methods, for which I would actually
include a separate Paragraph
2. The sentence "people living in the low levels of the society" though modified
from the first version is still - as mentioned by another Reviewer - incorrect and
inappropriate and should be changed to "people with low income"
3. "Although some may consider NCGS as a mild form of celiac disease" if there
are data on that, please add a citation. 
Section "Is there a Role for Mucosal Histology in the NCGS Diagnosis?"
In my previous review, I addressed 2 issues:
a. The Em/eo (Validated by Marsh/Oberhuber) versus the relatively new/non-
validated CD3 staining for the count of IELs, which may lead to falsely elevated
IEL counts in suspected celiac disease or non-celiac gluten sensitivity
b. the role of Helicobacter in increased intestinal lymphocytosis as possible
confounding factor in patients with gastrointestinal symptoms and suspected
non-celiac gluten sensitivity.
In the point by point answer the Authors say that the issues have been discussed
in the new version of the manuscript, yet I didn't find any mention of the two
topics. 
Section "Social and media aspect of choosing a GFD":
1. "Nutritional aspects are suggesting that the South Asian diet may be healthier
than the Western diet" please add citation
2. Table 2: the classification into pros and cons sounds substantially incorrect.
On one hand there are "conditions that may improve on a GFD according to
literature" and on the other hand "potential risks of a gluten free diet on
individuals without celiac disease", which I would not define as "pros and cons"
3. The topic of potential health risks of a GFD should be addressed more
carefully, considering existing data on the safety of a balanced GFD in celiac
disease
Section Conclusion
1. Line 389-391 "This change probably affects the gut microbiome, because the
gut microbiome of the two groups (wheat-containing and gluten-free diets) may
be different. This aspect may have, in turn, not irrelevant consequences for the
body and soul of individuals on this kind of diet." 
The effect of wheat/gluten on the microbiome will surely be the object of further
research, but the effect of a certain kind of diet on the soul of individuals should
probably never be mentioned in a scientific paper. I find the sentence arbitrary. 
Section Bibliography
1. As I mentioned when reviewing the first version of the manuscript, many of
the clinical trials cited in Table 1 are still not cited in the Bibliography (e.g.
Zanini 2015, Elli 2016, Di Sabatino 2015,...). it is important that 
all mentioned
studies be correctly cited in the Bibliography.
2. All in all, I think the Bibliography includes many other reviews (mainly
narrative reviews) as citations, I would appreciate more original works or
systematic reviews in order to directly access the source of the mentioned data. 
Publons Reviewer Recognition
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No
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
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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
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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
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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
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Reviewer’s report
Title: 
Non-Celiac Wheat Sensitivity: Rationality and Irrationality of a Gluten-
Free Diet in Individuals affected with Non-Celiac Disease
Version: 
1 
Date: 
28 Jun 2020
Reviewer's report:
I appreciated some of the changes to the Manuscript in order to clarify some
aspects and improve readability. 
However, there still are some issues that need to be addressed:
1. The term "gluten sensitive enteropathy" should not be used instead of celiac
disease (as suggested by the Oslo consensus on celiac disease terminology), it
confounds the reader adding yet another term, especially in a review focused on
the specificity of non-celiac gluten sensitivity. Later in the text other
confounding expressions such as "a non-GSE celiac symptomatologic pattern"
(Page 4 line 88-89) are used. I strongly suggest to use 
of the term "celiac
disease" only. 
Section Background: 
1. it is a shortened a easier to read introduction, but it starts with celiac disease
and its peculiarities and not with non-celiac gluten sensitivity, thus puzzling the
reader a bit. I suggest to start directly with the topic of the review itself. 
2. The following sentences are not quite clear and unnecessary lengthy (if the
aim is to express the concept that there are patients with suggestive symptoms
who don't have celiac disease):
"However, several patients may present with the symptomatology of the celiac
disease. Still, both biochemical values of anti-tissue transglutaminase antibodies
(ATTG), as well as duodenal histology, are probably unremarkable at first
glance. Confronted with this situation and struggling with the patients'
complaints, the gastroenterologist tries to have refuge in further diagnostic tests
or more complicated levels of genetic diagnosis.". 
Section Main text: 
1. The main text abruptly starts with the Methods, for which I would actually
include a separate Paragraph
2. The sentence "people living in the low levels of the society" though modified
from the first version is still - as mentioned by another Reviewer - incorrect and
inappropriate and should be changed to "people with low income"
3. "Although some may consider NCGS as a mild form of celiac disease" if there
are data on that, please add a citation. 
Section "Is there a Role for Mucosal Histology in the NCGS Diagnosis?"
In my previous review, I addressed 2 issues:
a. The Em/eo (Validated by Marsh/Oberhuber) versus the relatively new/non-
validated CD3 staining for the count of IELs, which may lead to falsely elevated
IEL counts in suspected celiac disease or non-celiac gluten sensitivity
b. the role of Helicobacter in increased intestinal lymphocytosis as possible
confounding factor in patients with gastrointestinal symptoms and suspected
non-celiac gluten sensitivity.
In the point by point answer the Authors say that the issues have been discussed
in the new version of the manuscript, yet I didn't find any mention of the two
topics. 
Section "Social and media aspect of choosing a GFD":
1. "Nutritional aspects are suggesting that the South Asian diet may be healthier
than the Western diet" please add citation
2. Table 2: the classification into pros and cons sounds substantially incorrect.
On one hand there are "conditions that may improve on a GFD according to
literature" and on the other hand "potential risks of a gluten free diet on
individuals without celiac disease", which I would not define as "pros and cons"
3. The topic of potential health risks of a GFD should be addressed more
carefully, considering existing data on the safety of a balanced GFD in celiac
disease
Section Conclusion
1. Line 389-391 "This change probably affects the gut microbiome, because the
gut microbiome of the two groups (wheat-containing and gluten-free diets) may
be different. This aspect may have, in turn, not irrelevant consequences for the
body and soul of individuals on this kind of diet." 
The effect of wheat/gluten on the microbiome will surely be the object of further
research, but the effect of a certain kind of diet on the soul of individuals should
probably never be mentioned in a scientific paper. I find the sentence arbitrary. 
Section Bibliography
1. As I mentioned when reviewing the first version of the manuscript, many of
the clinical trials cited in Table 1 are still not cited in the Bibliography (e.g.
Zanini 2015, Elli 2016, Di Sabatino 2015,...). it is important that 
all mentioned
studies be correctly cited in the Bibliography.
2. All in all, I think the Bibliography includes many other reviews (mainly
narrative reviews) as citations, I would appreciate more original works or
systematic reviews in order to directly access the source of the mentioned data. 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
No
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
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
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: 
1 
Date: 
28 Jun 2020
Reviewer's report:
I appreciated some of the changes to the Manuscript in order to clarify some
aspects and improve readability. 
However, there still are some issues that need to be addressed:
1. The term "gluten sensitive enteropathy" should not be used instead of celiac
disease (as suggested by the Oslo consensus on celiac disease terminology), it
confounds the reader adding yet another term, especially in a review focused on
the specificity of non-celiac gluten sensitivity. Later in the text other
confounding expressions such as "a non-GSE celiac symptomatologic pattern"
(Page 4 line 88-89) are used. I strongly suggest to use 
of the term "celiac
disease" only. 
Section Background: 
1. it is a shortened a easier to read introduction, but it starts with celiac disease
and its peculiarities and not with non-celiac gluten sensitivity, thus puzzling the
reader a bit. I suggest to start directly with the topic of the review itself. 
2. The following sentences are not quite clear and unnecessary lengthy (if the
aim is to express the concept that there are patients with suggestive symptoms
who don't have celiac disease):
"However, several patients may present with the symptomatology of the celiac
disease. Still, both biochemical values of anti-tissue transglutaminase antibodies
(ATTG), as well as duodenal histology, are probably unremarkable at first
glance. Confronted with this situation and struggling with the patients'
complaints, the gastroenterologist tries to have refuge in further diagnostic tests
or more complicated levels of genetic diagnosis.". 
Section Main text: 
1. The main text abruptly starts with the Methods, for which I would actually
include a separate Paragraph
2. The sentence "people living in the low levels of the society" though modified
from the first version is still - as mentioned by another Reviewer - incorrect and
inappropriate and should be changed to "people with low income"
3. "Although some may consider NCGS as a mild form of celiac disease" if there
are data on that, please add a citation. 
Section "Is there a Role for Mucosal Histology in the NCGS Diagnosis?"
In my previous review, I addressed 2 issues:
a. The Em/eo (Validated by Marsh/Oberhuber) versus the relatively new/non-
validated CD3 staining for the count of IELs, which may lead to falsely elevated
IEL counts in suspected celiac disease or non-celiac gluten sensitivity
b. the role of Helicobacter in increased intestinal lymphocytosis as possible
confounding factor in patients with gastrointestinal symptoms and suspected
non-celiac gluten sensitivity.
In the point by point answer the Authors say that the issues have been discussed
in the new version of the manuscript, yet I didn't find any mention of the two
topics. 
Section "Social and media aspect of choosing a GFD":
1. "Nutritional aspects are suggesting that the South Asian diet may be healthier
than the Western diet" please add citation
2. Table 2: the classification into pros and cons sounds substantially incorrect.
On one hand there are "conditions that may improve on a GFD according to
literature" and on the other hand "potential risks of a gluten free diet on
individuals without celiac disease", which I would not define as "pros and cons"
3. The topic of potential health risks of a GFD should be addressed more
carefully, considering existing data on the safety of a balanced GFD in celiac
disease
Section Conclusion
1. Line 389-391 "This change probably affects the gut microbiome, because the
gut microbiome of the two groups (wheat-containing and gluten-free diets) may
be different. This aspect may have, in turn, not irrelevant consequences for the
body and soul of individuals on this kind of diet." 
The effect of wheat/gluten on the microbiome will surely be the object of further
research, but the effect of a certain kind of diet on the soul of individuals should
probably never be mentioned in a scientific paper. I find the sentence arbitrary. 
Section Bibliography
1. As I mentioned when reviewing the first version of the manuscript, many of
the clinical trials cited in Table 1 are still not cited in the Bibliography (e.g.
Zanini 2015, Elli 2016, Di Sabatino 2015,...). it is important that 
all mentioned
studies be correctly cited in the Bibliography.
2. All in all, I think the Bibliography includes many other reviews (mainly
narrative reviews) as citations, I would appreciate more original works or
systematic reviews in order to directly access the source of the mentioned data. 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
No
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
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
assistant