Physiology in Medicine: a Series of Articles Linking Medicine with Science

Ulcerative colitis and Crohn disease are collectively called the inflammatory bowel diseases (IBDs) because of such similarities as a chronic remitting and relapsing course, their inflammatory nature, and their unknown causes. Nevertheless, these 2 disorders are clearly separated by distinct clinicopathologic features, including different locations within the gastrointestinal tract, diverse histologic patterns of inflammation, and the various disease-specific complications. Data that diverge from the traditionally accepted view of the pathogenesis of IBDs have recently been published (1). This new information has substantially challenged our conception on the pathophysiology of IBD and has complicated what was originally believed to be a simple dichotomy between Crohn disease and ulcerative colitis. According to the currently accepted hypothesis, ulcerative colitis and Crohn disease result from a dysregulated response of the mucosal immune system toward intraluminal antigens of bacterial origin in genetically predisposed persons (2–4). However, this hypothesis has been challenged by unexpected results from animal models of intestinal inflammation, which have led investigators to reject traditional pathogenetic concepts of these diseases (5, 6). Such animal models allow experimental manipulations that cannot be done in humans and are frequently used to test the efficacy of candidate therapies. In this review, we present emerging pathophysiologic concepts and discuss their effect on the classical paradigms for IBD.