Randomised Controlled Trial

Effects of Gluten-free Diet on Symptoms and the Gut Microenvironment in Irritable Bowel Syndrome

Joost P. Algera; Maria K. Magnusson; Lena Öhman; Stine Störsrud; Magnus Simrén; Hans Törnblom


Aliment Pharmacol Ther. 2022;56(9):1318-1327. 

In This Article

Abstract and Introduction


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 gluten-free diet in IBS

Methods: Twenty patients with IBS and 18 healthy controls (HC) followed a gluten-free 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 gluten-containing 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. Clinicaltrials.gov: NCT03869359.


The majority of irritable bowel syndrome (IBS) patients relate their symptoms to intake of certain foods.[1] The gut microenvironment, where microbiota, food components and the nervous system interact, is suggested to play a key role in gastrointestinal (GI) symptom generation in a subset of IBS patients.[2] Currently, dietary treatments focus on excluding specific food components, for example, gluten. Somewhat conflicting and heterogeneous results have emerged when assessing the gluten-free diet in IBS.[3] Therefore, the effects of gluten on GI symptoms in IBS patients still remain unclear.

Although a recent study has shown that exclusion diets have an effect on the gut microbiota in IBS,[4] it has not been investigated whether a gluten-free diet influence the microbiota composition differently in IBS patients and healthy controls (HC). Furthermore, gut microbiota metabolism utilising food components results in a large variety of metabolites,[5] which are suggested to be of importance for gut function and play a role in visceral hypersensitivity in IBS.[5] The effects of the gluten-free diet on the gut metabolite composition have not been determined in IBS patients.

This study investigated the hypothesis that a gluten-free diet can reduce GI symptoms in a subset of IBS patients through alterations in the gut microenvironment. Therefore, the primary aim of the study was to assess and compare the efficacy of the gluten-free and gluten-containing diets in terms of effects on GI symptoms in IBS patients. Secondary aims were to identify the putative link between gut microenvironment and the diets' effect on GI symptoms, and to identify potential predictors of clinical response to the gluten-free diet.