Review for 10.1186/s12876-020-01568-6 (2021)

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: 
20 Apr 2020
Reviewer's report:
I reviewed with great interest the manuscript by Consolato et al, entitled "Non-
Celiac Gluten Sensitivity / Non-Celiac Wheat sensitivity: Rationality and
Irrationality of a Gluten-Free Diet in Individuals affected with Non-Celiac
Disease". The manuscript is a comprehensive review in a topic of great interest
not only in the field of medicine, but to the general population. 
I would like to raise some comments related to the manuscript:
1- Title: The title is attractive. I would like to suggest a minor grammatical
change , to replace "..in individuals affected with non-celiac" by 
"individuals
without celiac disease or in non-celiac individuals" 
2- Abstract: 
-It is unclear what the authors means in the following sentence "This data was
implemented by the personal experience of a gastroenterologist (AC), a
pathologist (VV), and a pediatrician and pediatric pathologist (CS)" ; did the
authors mean that they performed a critical appraisal of the literature for this
review? Please clarify. 
3- Core section: It is unclear what the purpose of this section is, as it is mostly
based on the pathology findings described for NCGS. 
It would be appropriate if
this review was centered in pathology, but this is not expressed anywhere. 
4- Background:
- The background starts with description of celiac disease, however, this is
extended for over 2 pages. It is reasonable to include celiac disease as part of
gluten related disorders; however, this seems extensive and unnecessary as this
review should be focused in NCGS/NCWS. Perhaps it should be shorten? 
- Line 126: please describe what "celiac symptoms" means. Do the authors mean
gastrointestinal symptoms?
- Lines 140-143: It is unclear what the authors mean in these sentences. Please
clarify or rephrase if possible. 
- Line 153: Please describe allergy to which cereals; do the authors means wheat
or other cereals? 
- Line 162: The reader may not be familiar with some of the terms used in the
review. For example, the term christchurch site? 
. Please provide further
information and reference if possible.
- Lines 222-231: This paragraph discusses again the definition of celiac disease
by Oslo consensus. This seems out of context, as this review is on NCGS. This
could be moved up to the beginning of the background or removed. 
- Lines 273-275: 
the following sentence: "Most of the work on the topic of
NGCS considers the duodenal mucosa healthy or almost healthy without
indicating morphological aspects useful for identifying the condition considering
it often useless" . Perhaps this sentence can be rephrased, as biopsy is used to
rule out celiac disease or other disorders; rather than confirming NCGS/NCWS.
- Line 303-304: the following sentence "Overall, these data could indicate that
NCWS is an inflammatory condition which involves the entire gastrointestinal
tract..." seems misleading, as there is no evidence that NCWS/NCGS involves
the entire GI tract. Please rephrase accordingly. 
- Lines 318-319: The authors mention animal models to evaluate alterations in
immune tolerance to dietary antigens. It would be ideal to provide further
information on how animal models have contributed to this and what where the
findings; with their respective reference/s. 
- Line 388: Please clarify which "several conditions" the individuals may be
exposed to. 
5- Conclusion: 
- The description of the histological changes seems repetitive. They were already
described in core, and main text. Perhaps what could be useful as a
conclusion/discussion is the clinical application of these findings. Is this
pathognomonic of NCGS/NCWS? Does this mean that we need biopsy for all
patients with NCGS/NCWS to find these histological changes? 
- Line 428-429. The authors describe NCGS/NCWS as a "rare disease" ;
however, this seems controversial with the previous exposed concepts on
challenges in assessing the true prevalence of NCGS/NCWS, and also, with the
current studies describing a prevalence up to 6% of the general population. 
6- General comments:
- The review is very comprehensive; however, I found some difficulties with the
flow, and concepts were mixed in the 18 pages-main text. Perhaps the authors
would consider to re-organize the review in different sections; for example some
areas that I have identified in the manuscript are related to: 1- pathophysiology
and triggers and controversies it is FODMAPS or gluten?; 2- clinical
presentation 3- diagnosis;- Histology in NCGS/NCWS 4-Influence of culture in
choice to start GFD and challenges to establish the prevalence of NCGS/NCWS;
5- Pros and cons of following a GFD .
- The manuscript will benefit from English grammar revision; especially the
following sentences: 
- A) line 117 :" ..or wheat-containing food in a patient who has been ruled out to
have either celiac disease or wheat allergy" can be replaced by 
…" in patients in
whom celiac disease or wheat allergy have been ruled out". 
- B) Line 124: " low levels of the society" 
by " low income"
- C) Line 287 : " perspective" by "prospective" 
- D) line 296: "by the wheat ingestion" by " the ingestion of wheat"
- E) lines 375-380: this sentence include at least 2 concepts, and may be easy to
read if split by each concept. Please provide reference for each sentence. 
- References are missing in several sentences and sometimes in whole
paragraphs. For example lines : a) 120-123; b) 134-136; c) 161-173; d) 181-193;
e) 269-271; f) 297-301: does reference 38 corresponds here? If yes, please move
it up; g) 354-357 this sentence has been reported in several reviews and needs
reference; h)366-368 i)369-372; j) 389-394; k)397-400; 
- The terms NCWS , NCGS/NCWS were used indistinctly. It would easier to
follow if one term was used throughout the text for consistency. NCWS/NCGS
seems more inclusive, but of course, this is up to the authors. 
- The term "taxonomy" was used couple of times in the manuscript. Do the
authors mean classification? 
- 
Thank you for allowing me review this interesting manuscript and I hope the
authors find my comments helpful.
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
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organization that holds or has applied for patents relating to the content of
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paper?
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