FODMAPs, but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial

Background Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. Objective The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS severity scoring system (IBS-SSS). Methods The study was carried out with a double-blind, placebo-controlled, randomized three-way crossover design in a clinical facility in Uppsala in September 2018-June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomized; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomized to one-week interventions with FODMAPs (50 g/day), gluten (17.3 g/day), or placebo, separated by one week washout. All participants who completed at least one intervention were included in the intention-to-treat analysis. Results In participants with IBS (n = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI 222, 257]) than placebo (198 [180, 215]; 0.00056) or gluten (208 [190, 226]; P = 0.013); no differences were found between the placebo and gluten groups (P = 1.0). There were large inter-individual differences in IBS-SSS scores associated with treatment. No adverse events were reported. Conclusion In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large inter-individual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. Trial registration www.ClinicalTrials.gov (NCT03653689).