1 in 10 People Without Celiac Disease Report Gluten or Wheat Sensitivity

A recent study found that 1 in 10 people without celiac disease or wheat allergy report sensitivity to gluten or wheat.1

“Self-reported NCGWS was significantly more prevalent among females and was associated with anxiety, depression, and IBS,” wrote study investigator Mohamed G. Shiha, PhD, from the University of Sheffield in the UK, and colleagues.1

Investigators conducted a systematic review and meta-analysis to estimate the global prevalence and clinical characteristics of non-celiac gluten or wheat sensitivity (NCGWS), a condition defined by gastrointestinal and extraintestinal symptoms triggered by gluten or wheat ingestion in individuals without celiac disease or wheat allergy.1 The primary outcome was the global prevalence of self-reported NCGWS in the general population, while secondary outcomes included symptom prevalence, gluten/wheat avoidance, sex-based differences, and associations with irritable bowel syndrome IBS).

Investigators searched MEDLINE, Embase, Scopus, and Web of Science for relevant population-based studies, excluding hospital-only samples, gluten-challenge trials, case reports, editorials, and guidelines. In total, 25 studies published between 2014 and 2024 were included, encompassing 49,476 participants from 16 countries across 5 WHO regions: America, Europe, Western Pacific, South-East Asia, and Eastern Mediterranean.

The analysis revealed the pooled global prevalence of self-reported NCGWS was 10.3% (95% CI, 7.0 to 14.0%), with high heterogeneity (I² = 99.7%). Sensitivity analysis confirmed the stability of these estimates, which ranged from 9% to 11%.

Subgroup analyses showed prevalence rates varied significantly between countries (P <.001) and WHO regions (P <.001). Participants from high-income countries were more likely to self-report NCGWS than those in middle-income countries (P =.002). No significant difference emerged between adult and pediatric populations (P =.11).

A meta-regression analysis adjusted for covariates demonstrated that a greater proportion of females was associated with a significant increase in self-reported NCGWS prevalence (P =.02). Females had a 14% pooled prevalence of self-reported NCGWS (95% CI, 9.0% to 19.1%) compared to 7.6% (95% CI, 3.6% to 11.6%) in males. Ultimately, females were significantly more likely than males to report NCGWS (odds ratio [OR], 2.29; 95% CI, 1.80 to 2.90; P <.001).

However, only 17 studies reported sex-based differences in NCGWS prevalence and heterogeneity remained high (I2=79.0%). No significant associations were observed for total sample size (P =.35), year of publication (P =.33), country (P =.06), WHO region (P =.11), and number of participants with IBS (P =.78).

As for clinical characteristics, the study found bloating was the most frequently reported gastrointestinal symptom (71%), followed by abdominal discomfort (46%), abdominal pain (36%), constipation (26.1%), diarrhea (20.8%), and nausea (13.4%). Among extraintestinal symptoms, fatigue (32.1%) was the most frequently reported, followed by headache (18.2%), arthralgia (9.8%), and rash (7.3%).

Individuals with NCGWS were significantly more likely to report anxiety (OR, 2.95; 95% CI, 1.56 to 5.57; P <.001) or depression (OR, 2.42; 95% CI, 1.80 to 3.24; P <.001) than controls. Two studies also linked NCGWS to elevated psychological distress, with ORs ranging from 1.50 to 2.24.

Approximately 28% of individuals with NCGWS reported IBS-type symptoms (95% CI, 21.0% to 35.2%), with 4-fold greater odds than controls (OR, 4.38; 95% CI 3.34 to 5.75; P <.001). Gluten avoidance was common, with a pooled prevalence of 40%, and about one-third (32%; 95% CI, 17.2% to 46.8%) reported a physician diagnosis of NCGWS.

Despite its prevalence, NCGWS remains difficult to diagnose. Although the Salerno Expert’s criteria recommend a double-blind, placebo-controlled, crossover gluten challenge as the gold standard diagnostic method, studies using this approach have found that only a small proportion of patients exhibit true gluten-specific reactions.2,3 Given these diagnostic challenges, Shiha and colleagues emphasized the need to refine how NCGWS is understood and classified.1

“Our findings have implications for clinical practice and research,” investigators concluded.1 “To date, most research and funding have been focused on the role of gluten in triggering symptoms in NCGWS or on the search for specific disease biomarkers. Reclassifying NCGWS as a [Disorder of Gut-Brain Interaction] and the development of standardized symptom-based criteria for diagnosis could shift the focus toward a more holistic, biopsychosocial understanding of this heterogeneous condition…Future research should prioritize identifying the clinical phenotypes of NCGWS, exploring the role of the gut–brain axis and psychological comorbidities, and evaluating the effectiveness of multidisciplinary interventions beyond the gluten-free diet.”

References

1. Shiha MG, Manza F, Figueroa-Salcido OG, et al. Global prevalence of self-reported non-coeliac gluten and wheat sensitivity: a systematic review and meta-analysis. Gut. Published online October 28, 2025. doi:10.1136/gutjnl-2025-336304

2. Catassi C, Elli L, Bonaz B, et al. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria. Nutrients. 2015;7(6):4966-4977. Published 2015 Jun 18. doi:10.3390/nu7064966

3. Molina-Infante J, Carroccio A. Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials. Clin Gastroenterol Hepatol. 2017;15(3):339-348. doi:10.1016/j.cgh.2016.08.007