Fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial

Abstract

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).

Modest Conformity Between Self-Reporting of Bristol Stool Form and Fecal Consistency Measured by Stool Water Content in Irritable Bowel Syndrome and a FODMAP and Gluten Trial

“…Data and samples were obtained from a double-blind, placebo-controlled, randomized 3-way crossover trial conducted in 2018–2019, comprising 110 people with IBS. In total, 103 people completed the trial (20): 90 women and 13 men, 46 ± 15 years of age, with a BMI 24 ± 4 kg/m 2 . All participants had severe to moderate IBS, diagnosed by a gastroenterologist according to the Rome IV criteria (1).…”

“…The trial was approved by the Ethics Review Board, Uppsala (2018/ 159), and registered at www.clinicaltrials.gov as NCT03653689. The study is described in detail elsewhere (20).…”

Diet and irritable bowel syndrome: an update from a UK consensus meeting

“…This study demonstrated significantly higher Gastrointestinal Symptom Rating Scale (GSRS) scores for individuals consuming fructans rather than gluten (p = 0.049) [28]. In addition, a recent double-blind placebo RCT in 110 patients with IBS demonstrated that consumption of FODMAPs led to modest increases in IBS-SSS compared to the consumption of gluten (240 vs 208, p = 0.013) [29]. However, a recent study in patients with IBS showed no correlation of GI symptoms with fructan intake [30].…”

Modulating the gut microenvironment as a treatment strategy for irritable bowel syndrome: a narrative review

“…Interestingly, the clinical response to a low FODMAP diet may be predicted by gut microbiota composition before the start of the dietary intervention (Bennet et al, 2018; Valdez-Palomares et al, 2021; Valeur et al, 2018), by high colonic methane and SCFA production (Eetemadi and Tagkopoulos, 2021), and by high saccharolytic fermentation activity (Zhang et al, 2021), supporting the importance of the gut microenvironment. However, not all studies have demonstrated a correlation between fermentation or gut microbiota profile and IBS symptoms (Table 4) or show substantial benefits in symptomatology (Nordin et al, 2022). In addition, even though a low FODMAP diet or β-GOS supplementation for 4 weeks have very similar effects on symptom improvement, discontinuation of a low FODMAP diet may lead to a faster reappearance of symptoms as compared to elimination of prebiotic β-GOS supplementation.…”

“…This entity is known as non-coeliac gluten/wheat intolerance and can overlap with IBS (Spencer et al, 2014). The exclusion of gluten from the diet has been shown to successfully improve IBS symptoms in subgroups of patients (Supplementary References: Gluten-free diet), but not all studies agree with this (Nordin et al, 2022). Interestingly, one study demonstrated that approximately one third of IBS patients who benefit from a gluten-free diet suffer from wheat sensitivity (Barmeyer et al, 2017), which may be triggered by high levels of the FODMAP fructan found in wheat (Spencer et al, 2014).…”