A Controlled Trial of Gluten-Free Diet in Patients With Irritable Bowel Syndrome-Diarrhea: Effects on Bowel Frequency and Intestinal Function

Abstract

Background & Aims Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD). Methods We performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8–negative and 11 HLA-DQ2/8–positive) and 23 on the GFD (12 HLA-DQ2/8−negative and 11 HLA-DQ2/8–positive. We measured bowel function daily, small bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells (PBMCs) following exposure to gluten and rice. We collected rectosigmoid biopsies from 28 patients, analyzed levels of mRNAs encoding tight junction proteins, and performed hematoxylin and eosin staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups. Results Subjects on the GCD had more bowel movements/day (P=.04); the GCD had a greater effect on bowel movements/day of HLA-DQ2/8–positive than −negative patients (P=.019). The GCD was associated with higher SB permeability (based on 0–2 hr levels of mannitol and lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8–positive than −negative patients (P=.018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of ZO-1 in SB mucosa and significant decreases in expression of ZO-1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8–positive patients. GCD vs GFD had no significant effects on transit or histology. PBMCs produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-a in response to gluten than rice (unrelated to HLA genotype). Conclusion Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8–positive patients. These findings reveal a reversible mechanism for the disorder.

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

“…However, global symptoms and abdominal pain worsened from the end of the run-in phase to day 7 of treatment [45]. Conversely, a single-center, controlled study of 45 patients with IBS-D showed that patients randomly assigned to a gluten-free diet had a significant decrease in daily stool frequency from baseline compared with a diet containing gluten after 4 weeks (P = 0.04) [42]. These results raise the possibility that the positive effect of a gluten-free diet in patients with IBS may be a nonspecific consequence of reducing the intake of FODMAPs, given that wheat is one of the possible sources of FODMAPs.…”

“…However, before entertaining a diagnosis of nonceliac wheat sensitivity, patients should be properly evaluated with celiac serological screening and an upper endoscopy with biopsies to rule out celiac sprue. Because studies have shown that a gluten-free diet can improve IBS symptoms, at least in some patients, nonceliac wheat sensitivity may comprise a subset of patients with IBS [40,42]. A gluten-free diet was also shown to improve IBS-related QOL from baseline in some patients with IBS [43].…”

“…fermentable oligo-, di-, and monosaccharides and polyols [FODMAPs]) are thought to play a role [41]. Results of controlled studies in patients with IBS receiving gluten-free diets have been mixed [42,45], with some suggesting that gluten contributes little to IBS symptomatology and that fructans contained in wheat are actually the culprits [45]. This was concluded in a double-blind, crossover trial of 37 patients with IBS with selfreported nonceliac wheat sensitivity who received a reduced FODMAP diet during a 2-week run-in phase before randomization to a diet high in gluten (16 g/d), low in gluten (2 g/d plus 14 g whey protein/d), or placebo for 7 days [45].…”

Gluten Sensitivity in Pediatrics: A Clinical Conundrum

“…A large Italian retrospective study on 920 adult patients with irritable bowel syndrome (IBS) demonstrated that 30 % were positive to a wheat double-blind placebo-controlled food challenge (DBPCFC) and therefore classified as NCGS (74 % suffering from multiple food sensitivities) [10 • ]. Finally, a recent study on patients with diarrhea predominant IBS suggested that gluten withdrawal improved stool frequency, while its administration negatively influenced intestinal permeability [11].…”

Factors Predicting Whom to Screen for Coeliac Disease in Patients with Diarrhoea Predominant Irritable Bowel Syndrome in Developing Countries

“…Studies suggest that the prevalence of CD is increased in individuals with IBS; however, evidence is conflicting, and current guidelines do not always recommend screening for CD in these individuals. Prevalence of biopsy-proved CD in cases meeting diagnostic criteria for IBS was more than 4-fold that in controls without IBS [3].With data showing that patients with IBS-D may benefit from gluten free diet (GFD), GFD is used with increasing frequency in IBS-D patients [4][5][6]. Although there is little harm beyond cost to a patient on a balanced GFD,CD may be overlooked and complications ignored.…”