title: Dysbiosis in Crohn's disease - Joint action of stochastic injuries and focal inflammation in the gut.
abstract: Gut homeostasis involves interrelated biological networks that include the immune system, specialized cells of the epithelium, such as Paneth and goblet cells, as well as triggers derived from the microbiota. Disruption of these homeostatic interactions may lead to the pathogenesis of inflammatory bowel diseases (IBD). To develop more targeted and individual treatments in Crohn's disease and ulcerative colitis, it becomes more and more important to link key mechanisms of the disease pathogenesis to distinct IBD subsets. For the first time, our laboratory demonstrated a causal role of the microbiota for the development of Crohn's disease (CD)-like ileitis, supporting the hypothesis that a non-infectious, dysbiotic microbial ecosystem harbors aggressive traits relevant for the induction of chronic inflammation in the disease-susceptible host (i.e. TNFΔAREmouse model). Despite a growing body of evidence claiming a primary role for Paneth cells in the pathogenesis of ileal CD, we showed in the TNFΔAREmouse model that Paneth cell failure or exhaustion is a secondary event to inflammation. Therefore, additional mechanisms may act synergistically to initialize the development of CD-like pathology. Hereby, we propose a novel hypothesis suggesting that individual development of dysbiotic communities is based on stochastic injury and focal inflammation of the epithelial lining that propagate radially, finally leading to an aggressive microbial milieu.
authors.affiliation: a Technische Universität München, Chair of Nutrition and Immunology , Freising , Germany.
authors.forename: Ludovica F
authors.initials: LF
authors.lastname: Buttó
authors.affiliation: a Technische Universität München, Chair of Nutrition and Immunology , Freising , Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Haller
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D003424:Crohn Disease / Q000276:immunology* / Q000382:microbiology*; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000276:immunology* / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000382:microbiology
keywords: Crohn's disease; Dysbiosis; IBD; TNFΔARE; inflammation; intestinal epithelial cells (IEC); microbiome; microbiota; stochastic injuries