S3038 Non-Celiac Wheat Sensitivity in Refractory Functional Dyspepsia and Irritable Bowel Syndrome: A Prospective, Randomized Study

Introduction: Non-celiac gluten/wheat sensitivity (NCGWS) is characterized by gastrointestinal and extra-intestinal symptoms triggered by gluten or wheat ingestion. Its symptoms often overlap with those of irritable bowel syndrome (IBS) and functional dyspepsia (FD), making diagnosis challenging. Limited data exist on the prevalence and predictors of NCGWS among patients with refractory IBS or FD. Methods: We conducted a prospective, multicenter, double-blind, placebo-controlled, crossover trial in India (Oct 2021–Mar 2023; CTRI/2021/10/037323). Adults aged 18–65 years with Rome IV-defined refractory IBS or FD, after excluding celiac disease, wheat allergy, and alarm features, were enrolled. The diagnostic protocol involved 2 steps. Step I: a 6-week strict gluten-free diet (GFD) under dietitian supervision, with weekly symptom, quality-of-life (QoL), and psychological assessments using validated tools. Responders (≥30% reduction in 1 to 3 key symptoms) proceeded to Step II: a randomized, double-blind, placebo-controlled gluten challenge (DBPCGC). Participants received gluten or placebo cookies (8 g/day) for 1 week, followed by a 1-week washout and crossover. NCGWS was diagnosed if symptoms worsened by ≥30% on gluten compared to placebo. Primary outcome was NCGWS prevalence; secondary outcomes included symptom/QoL changes post-GFD and predictors of NCGWS. Statistical analysis included intention-to-treat and multivariable regression. Results: Of 252 screened, 177 entered GFD phase; 154 completed it (mean age 41.9 ± 14.2 years; 53.2% male). Eighty-2 (52.3%) responded to GFD, of whom 77 underwent DBPCGC. Thirty-1 patients (20.1%) showed significant symptom worsening with gluten, confirming NCGWS. Independent predictors included female gender, FD-IBS overlap, headache, fatigue, and anxiety. GFD led to marked improvement in gastrointestinal, QoL, and psychological scores. No carry-over or sequence effects were noted. Conclusion: Approximately 1 in 5 patients with refractory IBS or FD met criteria for NCGWS using a structured DBPCGC. Identifying NCGWS enables targeted dietary therapy and reduces reliance on pharmacologic interventions. A supervised GFD significantly improved symptoms and QoL in responders, supporting the role of structured evaluation in select functional GI patients.