A gluten-free diet reduced stool frequency as well as small bowel permeability in irritable bowel syndrome patients without celiac disease.
The findings, published in the May issue of Gastroenterology, "support the need for further clinical intervention studies to evaluate the clinical effects of gluten withdrawal in patients with diarrhea-predominant IBS," reported Dr. Maria I. Vazquez-Roque and her colleagues.
Dr. Vasquez-Roque, of the Mayo Clinic’s Clinical Enteric Neuroscience Translational and Epidemiological Research Program, in Rochester, Minn., and her colleagues recruited 45 subjects (43 women) from a database of more than 800 patients with irritable bowel syndrome who had been evaluated at the Mayo Clinic.
All patients had diarrhea-predominant IBS (IBS-D), were not on a gluten-free diet prior to the study, and did not have celiac disease.
They were randomized to either a gluten-free diet or a gluten-containing diet for 28 days. Patients’ meals and snacks were ingested or prepared in the Mayo Clinical Research Unit, and study participants were asked to eat only the foods provided by the study dietitians during the entire study period, the authors wrote. Dietitians assessed diet compliance using direct questioning of participants.
After 28 days of the study, the investigators looked at several clinical and histologic markers.
First, they tallied stool frequency, and found that patients on the gluten-containing diet had more stools per day than gluten-free patients did (P = .04), with a 95% confidence interval for the absolute difference between number of stools per day at –0.652 to –0.015 (Gastroenterology 2013 Jan. 28 [doi: 10.1053/j.gastro.2013.01.049]).
"While the absolute difference in stool frequency is small, it is important to appreciate that this increased frequency is on a background of the typical increase in stool frequency (average 2.6 bowel movements/day at baseline) and consistency in patients with IBS-D," the authors wrote.
This effect was more pronounced in subjects who were HLA-DQ2 or 8 positive (95% CI, –1.005 to –0.092; P = .019), they added.
Next, the investigators looked at small bowel permeability.
They found increased small bowel permeability with gluten-containing diet patients relative to their gluten-free counterparts, based on both cumulative mannitol excretion levels and lactulose:mannitol ratio. Similarly, this effect was more pronounced in HLA-DQ2 or 8 positive patients.
"While the clinical significance of these changes in permeability is not demonstrated in the current study, the abundant experimental evidence from the published literature is that increased mucosal permeability enhances inflammation and leads to increased sensitivity," they wrote.
Finally, the authors looked at tight-junction mRNA expression.
"Alterations in intestinal permeability and jejunal mucosal tight junction (TJ) signaling have been described in IBS-D, including postinfectious IBS-D," they wrote.
They found that expressions of ZO-1, occludin, and claudin-1 mRNA in colonic mucosa were significantly lower with the gluten-containing diet, compared with the gluten-free patients, particularly in subjects with HLA-DQ2 or 8 positive status.
There were no significant variations in tight junction signaling in the small bowel mucosa.
The authors conceded several limitations to their study. For one, it "did not evaluate effects of gluten on the microbiome, afferent functions, or cytokine expression in the mucosal biopsies from patients before and after the interventions. These would be interesting parameters to include in future studies," they wrote.
Additionally, "our study does not specifically address the effects of gluten protein per se, and it is possible that other proteins in wheat flour may be responsible for the changes observed."
Nevertheless, "our data provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS," they concluded.
The researchers disclosed receiving funding for this study from the National Institutes of Health. One investigator also disclosed having received grants from Alba Therapeutics, maker of the drug larazotide, used in celiac disease.
