The pathogenesis of Crohn's disease in the 21st century.

Ten years ago Crohn's disease remained a highly complex disorder with an unknown aetiology and a poorly understood pathogenesis. Research in this field had repeatedly confirmed the presence of an activated intestinal immune system but the factors underlying this had not been identified. Since then, the significance of genetic susceptibility has been established and underlined by the discovery of the NOD2 gene. In turn, this has gone on to signal the importance of the innate immune system and the critical relationship between the gut flora and the intestinal mucosa. These factors, together with independent environmental triggers such as cigarette smoking, form the basis of Crohn's disease pathogenesis in the new century.