Microbial and Dietary Factors in the Pathogenesis of Chronic, Immune-Mediated Intestinal Inflammation
R. Balfour Sartor
Although genetic background is an important prerequisite for Crohn’s disease, ulcerative
colitis and experiment intestinal inflammation, yet to be identified environmental
factors profoundly influence genetic susceptibility. The influence of the environment is documented by the relatively low concordance of disease in identical twins, rapid changes in the incidence of idiopathic Inflammatory bowel diseases (IBD) in a given population within 3-4 decades, alterations in disease frequency following migration of a population to a new environment, and striking differences in aggressiveness and phenotype of experimental ileocolitis when a susceptible rodent colony is moved to a new environment or when their housing conditions are changed.1 Although environmental influences are complex, commensal enteric bacteria, episodic or persistent infections and the diet are the most obvious environmental factors capable of modulating genetic susceptibility to chronic immune-mediated intestinal inflammation.
The distal ileum and colon, which are the preferential sites of human IBD and experimental intestinal inflammation in susceptible rodents, are colonized with an incredibly complex mixture of predominantly anaerobic bacteria as well as commensal fungi2 (Table 1). Moreover, we are all intermittently exposed to self-limited enteric and systemic infections that can transiently induce intestinal inflammation, break the mucosal barrier, alter the balance of pro and anti-inflammatory cytokines and activate effector innate and cognate immune cells. In certain settings, persistent enteric pathogens can influence chronic gastrointestinal inflammation, as documented by the influence of Helicobacter pylori in peptic ulcer disease. To further increase the complexity of the intestinal microenvironment, certain subsets of bacteria preferentially adhere to the intestinal epithelial cells, others integrate into the mucus layers, thereby constituting a biofilm, while yet others appear to solely colonize the lumen.2-4 Moreover, certain bacterial species selectively colonize different intestinal regions. Thus, unfortunately, stool samples do not accurately reflect the mucosally associated organisms that most likely provide the adjuvants and antigens responsible for activating mucosal immune responses.