Chapter 8 - Gnotobiotics and Inflammatory Bowel Disease

Abstract

Inflammatory bowel diseases (IBD), of which Crohn's disease and ulcerative colitis are the predominant forms, afflict up to 1.5million people in the United States and 2.2million in Europe. Crohn's disease can affect any part of the gastrointestinal tract; however the ileum and proximal colon are the most common sites, and the inflammation tends to be granulomatous and transmural, whereas ulcerative colitis is confined to the colon and rectum, and the inflammation typically is limited to the mucosa. In either case, effects on quality of life are considerable, and there is increased risk of colon cancer. It is now generally accepted that the fundamental basis of IBD is dysregulated immune and inflammatory responses to specific antigens of certain autochthonous intestinal bacteria, due to genetic susceptibility factors and nongenetic risk factors or triggers. However, the etiology and pathogenesis of IBD are far from fully understood. The number of loci associated with IBD now exceeds 160, but how they act, or interact, to contribute to disease is unknown for most. Moreover, the concordance rate among monozygotic twins for Crohn's disease is 50% or less, and for ulcerative colitis it is 20% or less, indicating the substantial role of nongenetic factors, yet these also are largely unclear. Thus, IBD is exceedingly complex and will require continued major research efforts to understand.