While Agr2−/− mice in our colony developed severe spontaneous ileocolitis that resembles human inflammatory bowel disease (IBD),20 an independently generated Agr2−/− mouse model did not develop spontaneous inflammation despite increased susceptibility to experimentally induced acute colitis and a higher incidence of rectal prolapse at very old age.9 These results suggest the potential contribution of specific intestinal microbiota to increased severity of intestinal pathology and the development of spontaneous ileitis. Here, AGR2 is linked to ileocolitis.