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P041. Methyl donor deficiency affects small intestinal differentiation and barrier function in rats

A. Bressenot1, P. Shabnam1, C. Bossenmeyer-Pourie1, G. Gauchotte1, A. Germain1, J.‑B. Chevaux1, F. Coste1, J.‑M. Vignaud1, J.‑L. Guéant1, L. Peyrin-Biroulet1

1Medical faculty and CHU of Nancy, Nancy-Université, Inserm U954, Nancy, France

Background: Dietary methyl donors (vitamin B12 and folate) and their genetic determinants are associated with Crohn's disease risk. Crohn's disease can involve both colon and the small intestine. Methyl deficient diet (MDD) aggravates experimental colitis.

Methods: We investigated whether MDD may affect development and functions of small intestine in rat pups from dams subjected to the MDD during gestation and lactation. Two groups were considered (n = 10 for MDD and n = 8 for control animals). Cell organization, apoptosis, proliferation and differentiation were studied within proximal and distal small intestine mucosa of rats.

Results: A global wall hypotrophy was observed in distal small bowel with increased crypt apoptosis, loss of enterocyte differentiation in villous and reduction of intestinal phosphatase alkaline production. In both proximal and distal small bowel cleaved caspase‑3 immunostaining and Apostain labelling index showed increased crypt apoptosis. Decreased proliferation was observed in crypts of the proximal small bowel with a reduced number of MCM‑6 and Proliferating Cell Nuclear Antigen (PCNA)-positive cells. This lack of enterocyte differentiation in distal small bowel was associated to impaired expression of beta-catenin and decreased beta-catenin/E-cadherin interaction. Low Protein Phosphatase 2A expression levels may trigger increased beta-catenin degradation. MDD also affected intestinal barrier in proximal small bowel by decreasing Paneth cells number after immunostaining for lysosyme and by reducing goblet cells number and mucus production after immunostaining for mucin‑2.

Conclusions: Overall, MDD has dual effects on small intestine by producing dramatic effects on enterocyte differentiation and barrier function in rats. MDD might be a predisposing factor to small bowel Crohn's disease.