Resident enteric flora modulates the development of colitis in gnotobiotic mice

This dissertation provides in depth studies on how the composition of the resident intestinal microflora modulates the development of colitis in gnotobiotic mice. It is arranged into 4 sections including: (1) General introduction---this includes an overview of human inflammatory bowel disease (IBD) and a literature review of the host-microbial interactions contributing to IBD in humans and in experimental animals. In brief, this section provides strong scientific evidence that luminal bacteria are an important environmental factor in the development of intestinal inflammation in humans and animal models; and that bacterial species vary in their ability to incite mucosal inflammation in a susceptible host. This section also introduces our use of a novel gnotobiotic mouse model of intestinal inflammation utilized in the two attached research publications. (2) Paper 1---entitled Composition of the resident enteric flora modulates colitis in defined flora mice characterizes antigen-specific immune responses to a defined gastrointestinal flora in the pathogenesis of experimental colitis. Gnotobiotic mice possessing an altered schaedler flora were used to evaluate the host\u27s response following challenge with H. bilis and/or B. hyodysenteriae. These data indicate that the nature of the gastrointestinal flora significantly influences the immunologic bias of the immune response and the presence of Helicobacter species do not apriori predispose toward a Th1 immune response. (3) Paper 2---entitled Gnotobiotic mice colonized with Helicobacter bilis demonstrate antigen-specific immune responses to resident enteric flora investigates the kinetics of host responses to resident enteric flora following colonization with H. bilis. These data indicate that immunologic responses of gnotobiotic C3H mice colonized with H. bilis developed rapidly, persisted over the 10 week study period and were of mixed Th1:Th2 phenotype. Furthermore, we propose a potential pathogenic role for H. bilis in perturbing the normal resident microflora and inducing antigen-specific immune responses against multiple resident bacterial species which may predispose to colitis. (4) General Conclusions---provides an overall summary of the conclusions drawn from papers 1 and 2 and proposes future studies regarding host-microbial interactions mediating chronic intestinal inflammation