Study of the interaction between the gut flora and the mucosal immune system in the earliest lesions of Crohn's disease in the postoperative recurrence model.

Crohns disease (CD) is a chronic inflammatory bowel disease, with (bloody) diarrhea and abdominal pain as major symptoms. The pathogenesis of CD is still unknown, but its thought that the chronic intestinal inflammation in CD results from an inappropriate and ongoing activation of the mucosal immune system against the normal luminal microbiota in genetically susceptible persons, most likely facilitated by defects in both the intestinal epithelial barrier function and mucosal immune system. The critical feature in the pathogenesis of the disease is the interaction between the gut flora and the mucosa. Optimally one should be able to study this interaction at initiation of Crohns disease. The sequence of events leading to full blown Crohns disease can be studied in the model of early post-operative Crohns disease. Our group has shown that after ileal resection with ileocolonic anastomosis new Crohns lesions recur in the neo-terminal ileum within months to weeks. These early lesions develop only if there is exposure of this gut segment to luminal contents. When luminal fluid is diverted through a proximal stoma the gut mucosa remains intact. Infusion of intestinal contents through the diverted bowel triggers early changes consistent with recurrent inflammation. We have shown that early recurrence is also related to myenteric plexitis. Hence, the post-operative recurrence model is an excellent tool to study the etiopathogenesis of Crohns disease. The aim of the study is to unravel the sequence of events taking place at the time of development of early Crohns lesions focussing specifically on the interaction between the gut flora and the mucosal immune system. In that manner we want to identify new targets for therapy and develop strategies for prevention of recurrent lesions.

Keywords:Chrohn's disease, Post-operative recurrence model, Gut flora, Mucosal immune system

Disciplines:Gastro-enterology and hepatology