Review for 10.1186/s12876-025-03799-x (2025)

Title: Prevalence and Characteristics of Adults Avoiding Gluten Without Celiac Disease: A
Long- Term Population-Based Follow-Up Study
Version: 1 Date: 27 Feb 2025
Reviewer's report:
The prevalence of people avoiding gluten without celiac disease (PWAG) in Finland increased
from 0.2% in 2000 to 0.7% in 2011, with the highest prevalence observed in individuals over 70
years old. PWAG individuals were more likely to follow additional special diets, such as lactose-
free or allergy-related restrictions. While PWAG had higher depression scores in 2000, no
psychological differences were observed in 2011. No clear predictors, including celiac-related
risk factors, were identified for future gluten avoidance.
This is a well-written and structured manuscript.
The data presented in this report are interesting but require further details and clarification:
1. Title: Prevalence and Characteristics of People Avoiding Gluten Without Celiac Disease:
A Long-Term Population-Based Follow-Up Study. The title does not specify that the study
includes only adults over 29 years, which may create the false impression that children are also
included. Clarifying this would improve accuracy.
2. Exclusion of Children: There is no explanation for the exclusion of children (age 0–18 years)
from the study. If data from the nationwide Health 2000 and 2011 surveys on children (e.g.,
school-aged children) are available, their inclusion would add value and relevance to this article.
3. Recommendation to Include Studies on Children: I suggest incorporating studies on children
to provide a broader perspective on the topic. Relevant articles that can be cited include:
Devulapalli CS. Gluten-free diet in children: a fad or necessity? Arch Dis Child. 2021
Jul;106(7):628-629.
Devulapalli CS. Non-Celiac Gluten Sensitivity in Children: Controversial Role of Gluten
and Diagnostic Enigma. Hepatology and Gastroenterology 2021; 5(3), doi:10.21926/
obm.hg.2103059.
Devulapalli CS. Avoidance of gluten in children with non-celiac gluten sensitivity is debatable.
Japanese J Gastroenterol Res. 2021; 1(3):1014.
4. Unclear Sentence: The following sentence is unclear and possibly incomplete:"An additional
limitation was the somewhat dated nature of the data and modest amount of subject with PWAG
and newer nationally representative cohort studies on PWAG should be pursued."
Please rephrase for clarity.
5. Excessive Use of Abbreviations: The manuscript contains too many abbreviations, including
PWAG, CeD (Celiac Disease), TGA (Transglutaminase Antibodies), EmA (Endomysial
Antibodies), GHQ-12 (General Health Questionnaire), BDI (Beck Depression Inventory), CI
(Confidence Interval), IBS (Irritable Bowel Syndrome), and FODMAP. Reducing the use of
abbreviations where possible would enhance readability.
6. Lower Participation Rate in 2011: The authors mention that “Limitations were the lower
participation rate in 2011 compared to 2000, although this was statistically adjusted for, lack
of data on HLA genotype and family risk of CeD.” However, potential reasons for the lower
participation rate in 2011 are not discussed. Please elaborate.
7. Research on Pathological Mechanisms: The manuscript states, “More research is needed to
decipher the pathological mechanisms and the true causal role of gluten in PWAG.” To support
this point, the following article may provide relevant insights:
Devulapalli CS. Non-Celiac Gluten Sensitivity in Children: Controversial Role of Gluten
and Diagnostic Enigma. Hepatology and Gastroenterology 2021; 5(3), doi:10.21926/
obm.hg.2103059.
8. Introduction on Pathological Mechanisms: Given the importance of understanding the role
of gluten in non-celiac gluten sensitivity (NCGS/PWAG), a brief introduction on pathological
mechanisms would be appropriate.
9. Discussion on Gluten-Free Diet Trends: The authors write, “Although true biological causes
cannot be fully excluded, it is possible that the increase is at least partially explained by the hype
surrounding the perceived health benefits of dietary gluten avoidance.” This is an important
point, as factors such as the availability, marketing, and advertising of gluten-free products likely
contribute to this trend. Adding a sentence or two on this in the discussion section would be
valuable. Relevant articles include:
a. Devulapalli CS. Gluten-free diet in children: a fad or necessity? Arch Dis Child. 2021
Jul;106(7):628-629.
b. Devulapalli CS. Avoidance of gluten in children with non-celiac gluten sensitivity is
debatable. Japanese J Gastroenterol Res. 2021; 1(3):1014.
10. Supplementary Material: Table 1 in the supplementary material is unclear and possibly
incomplete. Please verify and revise if necessary.