Environment and Genes: What Is the Interaction?

Inflammatory bowel disease (IBD) results from a continuum of complex interactions between a quartet of host-derived and external elements that involve various aspects of the intestinal microbiota, the immune system that is centered around the intestinal epithelial cell barrier, the genetic composition of the host and specific environmental factors. Recent studies into the complexity of these arrangements increasingly support the syndromic nature of this disorder and involve a wide range of interacting biologic pathways that affect innate immunity, adaptive immunity, endoplasmic reticulum stress and autophagy as well as metabolic pathways associated with cellular homeostasis. It is further likely that all of the aforementioned host factors including the microbiota, which is as much a part of ourselves as is any organ system, are under the influence of yet-to-be-understood environmental factors that predispose to and precipitate IBD. Notwithstanding the importance of genetic predisposition, these environmental influences are no doubt central to disease pathogenesis in light of the rapid emergence of IBD throughout the world and assumption of disease in migrating populations from low to high risk environments. It can thus be anticipated that environmental factors that modify the risk for development of IBD have the common attribute of affecting the relationship between the commensal microbiota and the immune system in a manner that intersects with the functionally relevant immuno-genetic pathways, and potentially modifies them through epigenetic effects, in a manner that are uniquely operative within a particular syndromic context of IBD and occur sequentially and in a reiterative fashion, perhaps beginning in early life.