As noted in previous posts, gluten-free diets (GFDs) have become commonplace for individuals without celiac disease. Clinically, subgroups of patients with irritable bowel syndrome (IBS) were noted to have gluten sensitivity. But, these subgroups were difficult to define and the mechanisms of improvement with a GFD were purely speculative. A new study identifies changes in the frequency of bowel habits and mucosal permeability associated with a GFD among diarrhea-predominant IBS patients (Gastroenterol 2013; 144: 903-11).
While the investigators conducted a trial of short duration (4 weeks) and only enrolled 45 patients, they completed a number of sophisticated studies.
Design: 45 patients were randomized into either a gluten-containing diet (GCD, n=22) or GFD (n=23). In each group, there were 11 patients who were HLA-DQ2/8 positive.
- Daily bowel frequency
- Small bowel and colonic transit
- Mucosal permeability using lactulose/mannitol excretion. Lactulose is normally not absorbed except with increased permeability. Mannitol is passively absorbed throughout intestine. Higher lactulose:mannitol ratio in urine reflects intestinal permeability.
- Cytokine production
- Rectosigmoid biopsies (from 28 patients) to analyze messenger RNA for tight junction proteins and immunohistochemical staining
- Fewer bowel habits were noted in patients receiving GFD. In this group, bowel habits decreased from ~2.6/day to 2/day. This was significant compared with GCD group. Furthermore, this effect was more pronounced among patients positive for HLA-DQ2 or HLA-DQ8.
- There was no significant change in stool form or ease of passage between GFD and GCD groups.
- GCD had increased small bowel permeability as shown by mannitol excretion and lactulose-to-mannitol ratio (specific #s Table 1). Again, this effect was more pronounced among patients positive for HLA-DQ2 or HLA-DQ8.
- GCD group had a reduced mRNA expression of mucosal tight junction proteins.
- GCD was not associated with significant effects on colonic transit, immunocyte activation, or altered histology (eg. increased intraepithelial lymphocytes, change in crypt:villus ratio).
The increased changes in HLA-DQ2/HLA-DQ8 suggest a role for adaptive immune response in mediating GCD effects on barrier function.
Conclusion: “our data provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS.”
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