NOD2 and Cowden disease: Several arguments underline that intestinal bacteria play a crucial role in IBD pathogenesis: Inflammation in IBD is located in areas with a high density of bacteria (mostly colon and/or terminal ileum) [45]; germ free mice do not develop colitis [46]; exposure of fecal stream to the terminal ileum worsen inflammation [47]; antimicrobial peptides are insufficiently expressed in CD, and mutations of human receptors recognizing luminal bacteria, such as NOD2 [48],[49] and TLR dysfunction [50],[51] are linked to a higher risk of IBD development.