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 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.

FIGURE 1

Study design, randomised double‐blind placebo‐controlled crossover trial

FIGURE 2

Flow chart of responses to both gluten‐free diet (GFD) and gluten‐containing diet (GCD). (A) Six IBS patients responded to the gluten‐free intervention and did not respond to the gluten‐containing intervention and were identified as true responders (TR), and all others (n = 14) were identified as non‐responders (NON). (B) individual changes in IBS‐SSS during both GFD and GCD.

FIGURE 3

Effects of a 2‐week gluten‐free diet on fold changes (after/before gluten‐free intervention) in faecal microbiota (GA‐map™ dysbiosis test), shown as PCA scatterplots with centroids (A and B) and OPLS‐DA scatterplot (C) Permutation test for (C) showed no overfitting. IBS (n = 20), HC (n = 18), true responders (n = 6) and non‐responders (n = 14).

FIGURE 4

Effects of a 2‐week gluten‐free diet on fold changes (after/before gluten‐free intervention) in metabolites of faecal supernatants (LC–MS), shown as PCA scatterplots with centroids ( A and C) and OPLS‐DA scatterplots (B and D). The R ² Y value determines goodness of the fit and the Q ² value represents the predictive ability of the model; R ² Y ≥ 0.5 and Q ² ≥ 0.4 are considered satisfactory. Permutation tests for (B) and (D) showed no overfitting. IBS (n = 20), HC (n = 18), true responders (n = 6) and non‐responders (n = 14).

FIGURE 5

Prediction of response to gluten‐free diet in IBS, assessed before the gluten‐free intervention. Faecal microbiota profiles (GA‐map™ dysbiosis test) shown as PCA scatterplot with centroids (A), and OPLS‐DA scatterplot (B). Metabolite profiles of faecal supernatants (LC–MS) shown as PCA scatterplot with centroids (C), and OPLS‐DA scatterplot (D). The R ² value determines goodness of the fit and the Q ² value represents the predictive ability of the model; R ² Y ≥ 0.5 and Q ² ≥ 0.4 are considered satisfactory. Permutation test for (D) showed no overfitting. True responders (n = 6) and non‐responders (n = 14).