Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318281f573
Original Basic Science Article

Semisynthetic Diet Ameliorates Crohn’s Disease–Like Ileitis in TNFΔARE/WT Mice Through Antigen-Independent Mechanisms of Gluten

Wagner, Stefan J. MSc*; Schmidt, Annemarie MSc*; Effenberger, Manuel J. P. BSc*; Gruber, Lisa MSc*; Danier, Jürgen MSc; Haller, Dirk PhD*

Supplemental Author Material
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Background: Enteral nutrition is used to treat a subset of patients with inflammatory bowel diseases. Because dietary factors may contribute to an aggressive immune response toward the intestinal microbiota in the disease susceptible host, we used TNFΔARE/WT mice to study the therapeutic effect of a semisynthetic experimental diet in the pathogenesis of Crohn’s disease (CD)–like inflammation in the ileum.

Methods: TNFΔARE/WT mice were fed chow and experimental diets partially fortified with gluten in a dose and time-dependent manner. Histopathology, markers of inflammation, intraepithelial lymphocytes phenotypes, and antigen-specific reactivation of CD4+ T cells were determined.

Results: TNFΔARE/WT mice being transferred to an experimental diet with 7 but not with 10 or 14 weeks of age were protected from development of Crohn’s disease–like ileitis. Although disease-related CD8αβ+ intraepithelial lymphocytes were increased irrespective of dietary intervention, the protective effect of experimental diet was associated with decreased expression of inflammation markers in ileal tissues. In addition, CD4+ T-cell reactivation in bacterial antigen-primed dendritic cell cocultures was not altered between semisynthetic and chow diet-fed TNFΔARE/WT mice, suggesting bacteria-independent mechanisms. Most importantly, gluten-fortified experimental diet induced chronic ileitis in TNFΔARE/WT mice, despite the fact that gluten-derived peptides failed to induce CD4+ T-cell activation. Reduced occludin expression levels suggest a negative role of gluten-fortified experimental diet on intestinal barrier integrity.

Conclusions: Crohn’s disease–like ileitis can be prevented at early stages of disease development using a semisynthetic experimental diet. Gluten was identified as antigen-independent dietary factor relevant for the induction of chronic inflammation in the small intestine of TNFΔARE/WT mice.

© Crohn's & Colitis Foundation of America, Inc.

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