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GRK 1482 Jahrbuch 2011-2014

Abstract The mammalian gut microbiota is crucial for the development of IBD. However, molecular mechanisms underlying microbiota/host interac- tions in ileal inflammation remain to be better characterized. The aim of our project is to assess the importance of the gut microbiota in experimental ileitis. We intend to test the impact of specific microbial triggers like HSP70 or complex pools of bacterial signaling molecules (caecal bacterial lysates) on the onset of ileal inflammation and shifts in the gut microbiota. Introduction Overthelastdecades,theincidenceofinflammatory bowel diseases (IBD), including Crohn’s disease (CD) and Ulcerative colitis, has been increasing in industrial countries. These diseases result from a complex pathogenesis driven by both genetic pre- dispositions and environmental factors like nutriti- on and the gut microbiota (i.e., all communities of microorganisms living in the intestine). The gut microbiota is a very complex and diverse ecosystem, which influences intestinal physiology and host immune responses. It is nowadays ack- nowledged that the development of IBD is cha- racterized by the loss of immunological tolerance towards commensal microorganisms and that intestinal inflammation is associated with shifts in the microbiota, referred to as dysbiosis. Additi- onally, intestinal inflammation is mostly located in areas with high microbial density and IBD patients tend to show higher density of mucosa-associated bacteria. These events speak in favor of the prima- ry role of gut bacterial in IBD. However, dominant microbial triggers influencing the development of chronic intestinal inflammation remain to be defi- ned, especially in the context of ileal inflammation. Based on the recent work by Sydora et al. (2011) in a mouse model of colitis, we proposed that neonatal intraperitoneal (i.p.) challenge of caecal antigens leads to reduced inflammation in the Tnf∆ARE/wt mouse model of CD-like ileitis. Moreover, bacterial heat-shock proteins (HSP) were shown to play an important role in various bacteria-driven infections, are dominant peptides in the gut, can mimic the actions of host molecular chaperones and thereby proved to be useful for the prevention of systemic chronic inflammation such as arthritis (Wieten et al., 2009). We thus also proposed that bacterial HSP play an important role in our experimental ileitis model. ASSOCIATED FELLOWS Page 66 | GRK Progress Report 2011-2014 Sarah Just (M.Sc.) Nutrition and Immunology PhD Gut microbial ecology in experimental IBD: towards the identification of bacterial triggers