Inflammatory bowel disease (IBD) is the term applied to a group of poorly understood intestinal disorders that commonly affect animals and people. IBD in both people and animals is increasingly considered a consequence of uncontrolled intestinal inflammation in response to a combination of environmental, enteric luminal constituents (principally microbial and dietary) and immunoregulatory factors in genetically susceptible individuals1.In people, genetic susceptibility is linked increasingly to defects in innate immunity exemplified by mutations in the innate immune receptor NOD2/CARD15, that in the presence of the enteric microflora may lead to up-regulated mucosal cytokine production, delayed bacterial clearance and increased bacterial translocation, thereby promoting and perpetuating intestinal inflammation2. More recently, genome-wide association studies have shown IBD-associated polymorphisms in pathways important for intracellular bacterial clearance (autophagy-related 16-like protein 1 (ATG16L1) and in genes regulating Th17 cell maturation and Th17 cytokines, which are upregulated in the mucosa of people with IBD3'4. Thus, the common theme emerging in IBD genetics involves the abnormal interfacing of innate immunity with intestinal microbes, leading to abnormal inflammatory cytokine production and clinical disease.
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