Gluten-Free Diet May Provide Benefits for Patients with Diarrhea-Predominant IBS

Although many patients with irritable bowel syndrome (IBS) follow a gluten-free diet, the relationship of “gluten exposure and symptom generation in irritable bowel syndrome (IBS) is complex and not well understood,” according to the authors of “A Controlled Trial of Gluten-Free Diet in Patients with Irritable Bowel Syndrome-Diarrhea: Effects on Bowel Frequency and Intestinal Function,” published in Gastroenterology.

To measure the effects of a gluten-free diet on bowel function in patients with diarrhea-predominant irritable bowel syndrome (IBS-D), researchers randomized 45 patients to follow either a gluten-containing diet (GCD) or gluten-free diet (GFD) for four weeks. Participants received three prepared meals per day plus snacks (macronutrient distribution of the meals was the same for both diets: 20% protein, 30% fat, and 50% carbohydrate). Compliance to the diet plan was assessed by “direct questioning by the dietitians when participants picked up the meal and snack supplies.”

The researchers assessed the effects of the GCD compared with a GFD on “bowel function, gut transit, small bowel (SB), and colonic barrier functions measured functionally by the 2-sugar excretion permeability test and messenger RNA (mRNA) expression of TJ proteins in the mucosa of the SB and rectosigmoid.”

They also assessed “mucosal morphology and immune activation in response to the diets, and the proliferative and cytokine responses of peripheral blood mononuclear cells (PBMCs) to gluten and rice antigens.”

Twenty-eight participants were examined by upper-gastrointestinal endoscopy and flexible sigmoidoscopy. During the study, all participants tracked bowel habits using a daily bowel pattern diary.

Primary end points for the study were:

• Colonic geometric center at 24 hours
• Urine mannitol excretion at 0—2 hours and 8–24 hours

Secondary end points were:

• Gastric emptying half-time (min)
• Colonic filling at 6 hours (%)
• Geometric center at 48 hours
• Ascending colon half-time
• Urine lactulose at 8—24 hours
• Urine lactulose:mannitol ratio at 0—2 hours and 8–24 hours
• Mucosal inflammation
• Bowel functions (frequency, consistency, ease of passage)

Demographics were similar for both groups (mean age in the early 40s, 95% female, BMI around 30, Hospital Anxiety and Depression scores).

Analysis of the data revealed a diet-related effect on stool frequency in the overall groups, with “a statistically significant decrease in subjects who were on a GFD compared with subjects on a GCD.” There was a more pronounced effect on stool frequency seen in participants who were HLA-DQ2 or 8 positive. Te researchers reported no significant diet-related effect on mean daily stool form or mean ease of passage score for either group.

There were also no significant dietary effects on gastric emptying and colonic filling at 6 hours for either group. The GFD group experienced no delay in colonic transit at 24 or 48 hours.

In their discussion of these results, the authors noted that participants on a GCD had increased stool frequency compared with a GFD, increased SB permeability, and reduced mRNA expression of mucosal TJ proteins. GCD “was not associated with significant effects on colonic transit, immunocyte activation, or intraepithelial lymphocytes in SB or colonic mucosa, or SB villus:crypt ratios.”

They concluded that these findings provide “mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS. The data also explain, in part, the observation of the relationship of HLA genotype to beneficial effects of gluten withdrawal in view of our results showing that biological effects of gluten were associated with HLA-DQ2 or HLA-DQ8 genotype.”