Introduction

Non-celiac gluten/wheat sensitivity (NCGWS) is characterized by gastrointestinal and extra-intestinal symptoms triggered by gluten/wheat ingestion. Symptoms of NCGWS overlap with those of irritable bowel syndrome (IBS) or functional dyspepsia (FD). Due to diagnostic challenges and symptom overlap, data on the prevalence and predictors of NCGWS among patients with IBS or FD, especially those with refractory symptoms, are limited.

Aims & Methods

This was a prospective, multicentric, double-blind, placebo-controlled, crossover trial conducted from October 2021 to March 2023 in India.This was prospectivly registered with the clinical trials Registry, INDIA (CTRI/2021/10/037323). Adults aged 18–65 years with Rome IV-defined irritable bowel syndrome (IBS) or functional dyspepsia (FD) refractory to standard treatment were enrolled after excluding celiac disease, wheat allergy, and alarm features. Participants underwent a two-step diagnostic protocol. In Step I, patients adhered to a 6-week strict gluten-free diet (GFD) under dietitian supervision. Weekly assessments of gastrointestinal and extra-intestinal symptoms, health-related quality of life (HRQoL), and psychological scores were performed using validated instruments. Gluten responders—defined by ≥30% reduction in one to three primary symptoms—were advanced to Step II: a randomized, double-blind, placebo-controlled gluten challenge with crossover. Subjects received indistinguishable gluten or placebo cookies (8 g/day) for one week, followed by a one-week washout and crossover. A ≥30% symptom difference between gluten and placebo phases confirmed non-celiac gluten/wheat sensitivity (NCGWS). Primary outcome was NCGWS prevalence; secondary outcomes included symptom and HRQoL changes post-GFD and predictors of NCGWS. Statistical analyses included intention-to-treat principles and multivariable regression to identify baseline predictors.

Results

Of the 252 patients screened, 177 were enrolled for 6-week GFD (step I), and 154 patients completed this phase (mean age 41.9±14.2 years, 53.2% males). Eighty two (52.3%) patients responded to GFD, of whom 77 entered step 2 (DBPCGC). Thirty one (20.1%) patients had significant symptom worsening on blinded gluten ingestion, suggesting the presence of NCGWS. Independent predictors of NCGWS were female gender, FD-IBS overlap, headache, fatigue, and anxiety. Significant improvements in gastrointestinal symptoms, health-related quality of life, and psychological scores were observed after GFD in responders. No significant impact of diet sequence was noted.

Conclusion

Introduction

Few studies have examined esophageal motility disorders in patients with type 2 diabetes operated with sleeve gastrectomy (SG) or gastric bypass (RYGB).

Aims & Methods

We have recently reported overall prevalence of gastroesophageal reflux disease (GERD) in this group of patients (1) and now aimed to investigate potential differences between the two surgical methods regarding the prevalence of dysmotility 5 years after surgery. Furthermore, we also aimed to analyse and report on the available GERD-data in detail.
In the Oseberg study (January 2013 – December 2022), 125 patients with BMI ≥ 35 kg/m² and type 2 diabetes were screened, sixteen patients were excluded or withdrew consent, leaving 109 patients allocated to SG (n=55) or RYGB (n=54). To assess reflux symptoms, GerdQ (Gastroesophageal reflux disease questionnaire) was completed. Gastroscopy and 24-hour pH monitoring were used to examine GERD. High-resolution manometry with the Chicago classification v3.0 was used to assess esophageal motility.

Results

At inclusion the average age was 47.7 years (SD 9.6), BMI was 42.3 kg/m2 (5.3), and 66% were women. At the 5-year follow-up, 29 (53%) patients in SG-group and 32 (59%) in RYGB-group underwent gastroscopy, 22 (40%) vs. 25 (46%) underwent 24-hour pH monitoring, 23 (42%) vs. 26 (48%) underwent manometry, and 42 (76%) vs. 42 (78%) completed GerdQ. The proportion of patients with GERD symptoms (GerdQ ≥8) was low in both groups, with a slightly lower prevalence after RYGB (2%) than after SG (14%). There was no difference in the prevalence of erosive esophagitis between the groups (38% in SG and 41% in RYGB), all findings with less advanced esophagitis (Los Angeles grades A and B), but one patient in each group had new onset Barrett's esophagus. The proportion of patients with pH<4 for more than 6% of the recording (Acid exposure time, AET) was significantly higher after SG compared with RYGB (59% versus 8%, p < 0.0001). Esophageal dysmotility was diagnosed in 14 (61%) after SG compared with 19 (73%) patients after RYGB. Most of these patients (n=22) had hypertensive or hypotensive lower esophageal sphincter (LES), with no difference between groups. The remaining 11 patients had ineffective esophageal motility (IEM) or elevated distal contractile integral (DCI). None of the patients with dysmotility reported swallowing difficulties or chest pain with food intake.

Conclusion

The Oseberg study demonstrates a high prevalence of asymptomatic esophageal dysmotility after SG or RYGB with uncertain clinical relevance. Furthermore, a seven times higher prevalence of pathological acid reflux after SG compared with RYGB was demonstrated, but the prevalences of erosive esophagitis and esophageal dysmotility were approximately similar between groups. Few of the examined patients reported GERD symptoms, hence objective assessment of GERD should be included in long-term follow-up after SG to detect and prevent the development of Barrett's esophagus, dysplasia, and adenocarcinoma.

References

1. Hauge JW et al., Effect of gastric bypass versus sleeve gastrectomy on the remission of type 2 diabetes, weight loss, and cardiovascular risk factors at 5 years (Oseberg): secondary outcomes of a single-centre, triple-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2025 Apr 1:S2213-8587(24)00396-6