What explains the geographical and historical variation in the incidence of inflammatory bowel disease?
The discontinuous inflammation of the GI tract with skip lesions has been described as a hallmark feature of CD. Segmental mucosal inflammation is characteristic of many infectious forms of colitis (eg, tuberculosis, cytomegalovirus infection, amoebiasis). CD might be considered as an atypical infectious disease in which the host responds inappropriately to some elements of the commensal microflora.42 44 56 57 The segmental nature of inflammation in CD could therefore be due to the topology of the commensal microflora colonisation and the topology of the immune response (eg, receptor expression levels) and their mutual interactions. This concept is supported by the finding that different bacterial species cause inflammation in different segments of the GI tract in IL10-deficient mice.58 Other factors such as the segmental nature of the vascular and nerve supply, regional variation in lymphatics and M cells, stasis of luminal contents, deficiency in α-defensin in the ileum59 and the pro
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