Inflammatory bowel disease: maladaptation of the vigilant genotype in a hyper-clean world?

Abstract

Children born of Asian Indian parents who are raised in environmentally hygienic Western societies appear to be highly prone to two diseases, ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel disease or IBD. These ethnically Indian children are similar to an inbred mouse strain, NOD/Lt. Mice of this strain remain diabetes-free when raised in standard mouse colonies, but develop an autoimmune diabetes at high rates when kept in pathogen-free environments. I propose that certain human habitats have, over eons, selected for "vigilant genotypes," wherein combinations of alleles at critical loci result in aggressive immune responses to pathogens. This genetic configuration is adaptive in the selective environment but maladaptive in more hygienic environments, resulting in dysregulated immune effectors. One manifestation of such dysregulation is organ-specific autoimmunity, such as IBD.