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009 GLUTEN SENSITIVITY, ION TRANSPORT AND NEUROMUSCULAR RESPONSES IN THE GUT: THE LINK BETWEEN CELIAC DISEASE AND IRRITABLE BOWEL SYNDROME EF Verdu, J Lu, PA Blennerhassett, CS David1, JA Murray2, DM McKay, XX Huang BACKGROUND & AIMS: Celiac disease (CD) is a chronic intestinal inflammatory condition that occurs in genetically susceptible individuals exposed to gliadin (G). CD may mimic irritable bowel syndrome (IBS), but the mechanism for this overlap is unclear. Here we investigate whether gliadin sensitivity, in the absence of mucosal atrophy, causes changes in gut function that may explain its ability to mimic IBS.
Intestinal Disease Research Program, McMaster University, Hamilton; 1Department of Immunology and 2Gastroenterology, Mayo Clinic, Rochester, USA
METHODS: HLA-DQ8 transgenic mice were injected ip with gliadin (500µg /0.02 mM acetic acid [AA]) in 50µg CFA. 7 days later, mice were gavaged with gliadin (2 mg /0.02 mM AA) weekly, for 3 weeks (G-G). Control groups consisted of a) non-sensitized mice (CFA) gavaged with gliadin, BSA or rice, b) gliadin-sensitized mice gavaged with BSA or rice (G-BSA, G-R). Acetylocholine (ACh) release by longitudinal myenteric plexus preparations, motility in vivo, small intestinal contractility in vitro, and epithelial ion transport were measured. Anti-gliadin antibodies, tissue cytokines and IEL counts after CD3 immunostaining were investigated.
RESULTS: There was no mucosal atrophy in G-G mice. However, macrophages, IELs and expression of IL-15 were increased. Increased ACh release from the myenteric plexus and retroperistalsis in vivo, muscle hypercontractility after electric field stimulation or carbachol challenge, were detected in G-G mice compared to controls. G-G mice also exhibited a two-fold increase in active ion transport, measured as increases in short circuit current after electric transmural stimulation, but not in response to carbachol.
CONCLUSIONS: At early stages of gliadin sensitivity, a pro-secretory state induced by cholinergic dysfunction may lead to altered water movements and dysmotility. This mechanism may underlie the generation of IBS-like symptoms in some patients with gliadin sensitivity, and explain how celiac disease can mimic irritable bowel syndrome.