Randomised controlled trial: effects of gluten‐free diet on symptoms and the gut microenvironment in irritable bowel syndrome

Abstract

Background: A gluten-free diet reduces symptoms in some patients with irritable bowel syndrome (IBS) through unclear mechanisms.Aims: To assess the effects of gluten-free versus gluten-containing diet on symptoms and the gut microenvironment, and to identify predictors of response to the glutenfree diet in IBS Methods: Twenty patients with IBS and 18 healthy controls (HC) followed a glutenfree diet during two 14-day intervention periods where they sprinkled either gluten (14 g/day) or rice flour powder over their meals. Primary outcomes included effects of the interventions on IBS symptoms (IBS-SSS) and bowel habits. Secondary outcomes included effects of gluten-free diet on faecal microbiota and metabolite profile.Results: IBS symptoms improved during the gluten-free (p = 0.02), but not the glutencontaining period, with no difference between the interventions. IBS patients reported fewer loose stools during the gluten-free intervention (p = 0.01). Patients with IBS and HC presented distinct metabolite profiles based on the effects of the gluten-free diet (p < 0.001). True responders (reduced IBS-SSS by ≥50 solely after gluten-free period) and non-responders were discriminated based on the effects of the gluten-free diet on the microbiota (p < 0.01) and metabolite profiles (p < 0.001).The response to the gluten-free diet could be predicted by the metabolite profile before the intervention (p < 0.001). Conclusions:A gluten-free diet may influence symptoms in a subset of patients with IBS, with a particular effect on bowel habits. A gluten-free diet seems to impact the gut microenvironment. Responsiveness to the gluten-free diet may be predicted by the metabolite profile. Clini caltr ials.gov: NCT03869359.

Exploration of differential responses to FODMAPs and gluten in people with irritable bowel syndrome- a double-blind randomized cross-over challenge study

“…IBS being a heterogenous condition and important molecular determinants were not included. One previous study identified response to a gluten free diet versus a gluten-containing diet, but that study was underpowered for such a sub-analysis of differential response (Algera et al, 2022 ).…”

“…Concerning gluten, one clinical trial with a gluten-free diet versus a gluten-containing diet reported that response to the gluten-free diet could be predicted by the metabolite profile at baseline, identification of metabolites was not presented. However, the study was underpowered (Algera et al, 2022 ). To date, there are no generally accepted recommendations for tailored nutritional advice in IBS (Bennet et al, 2020 ; Drossman, 2016 ).…”

“…There is currently also no universal data-analytical framework for identification of differential response to dietary interventions. Both univariate (Böhn et al, 2015 ; Colomier et al, 2022 ; Halmos et al, 2015 ; Schindler et al, 2021 ; Valeur et al, 2018 ) and machine learning algorithms (Algera et al, 2022 ; Bennet et al, 2018 ; Chumpitazi et al, 2015 ; Nybacka et al, 2021 ; Rossi et al, 2018 ; Staudacher et al, 2020 ; Vervier et al, 2021 ; Zhang et al, 2021 ) have been applied in IBS and dietary trials, using the predictors mentioned above. Robust machine learning algorithms (Saccenti et al, 2014 ) could overcome the issue with multiple testing in univariate models, known to be problematic in analyzing large-scale omics data (Saccenti et al, 2014 ).…”

Editorial: gluten‐free but not pain‐free in IBS—authors' reply

“…We thank Fitzpatrick and Halmos for their interest in our randomised controlled trial on the effects of gluten‐free diet (GFD) on symptoms and the gut environment in irritable bowel syndrome (IBS) 1,2 . Based on this study, no strong clinical recommendations are made regarding the GFD in IBS, and we agree that gut microbial patterns are exciting as a predictor for response to diet therapy.…”

Editorial: gluten‐free but not pain‐free in IBS

“…Objective markers for gluten‐associated symptoms are lacking. Algera and colleagues have attempted to provide a biomarker of symptoms in response to gluten in patients with IBS through analysis of faecal microbiota and metabolite profiles in patients with IBS administered gluten and rice (placebo) powder on a background gluten‐free diet 1 . Despite no overall difference in symptom scores between gluten and placebo, microbiota and metabolites profiles differed in six of 20 IBS subjects, who responded solely to gluten provocation compared to the other 14 subjects.…”