Chapter 23 - The Role of Endogenous Luminal Bacteria and Bacterial Products in the Pathogenesis of Experimental Enterocolitis and Systemic Inflammation

Abstract

Although ulcerative colitis and Crohn's disease appear to be the result of an unrestrained inflammatory response, the antigen(s) which initiate and perpetuate these chronic, relapsing disorders remain uncertain. Clinicians have a longstanding belief that the normal enteric microbial flora were somehow involved in the pathogenesis of these diseases because inflammation occurs in the distal ileum and colon, antibiotics and bowel rest benefit patients with Crohn's disease, and inflammatory bowel disease (IBD) patients have increased immune responses to ubiquitous luminal bacteria. Recent investigations using the older induced models of intestinal inflammation and new genetically engineered rodent models that develop spontaneous enterocolitis provide compelling evidence to support the hypothesis that normal luminal bacteria and their products can induce and perpetuate chronic intestinal and systemic inflammation in genetically susceptible hosts. This hypothesis is rational, given the high concentrations of predominantly anaerobic bacteria and bacterial components in the distal ileum and colon. Mucosal inflammation enhances mucosal uptake and systemic transport of luminal bacterial components and promotes secondary invasion of mucosal ulcers and fistulae by enteric bacteria. These phlogistic bacterial constituents activate mucosal phagocytic cells and lymphocytes to secrete proinflammatory cytokines and soluble inflammatory mediators and stimulate specific immune responses which perpetuate the inflammatory process. This chapter summarizes evidence generated in animal models of enterocolitis which supports this hypothesis.