Pro-inflammatory microbiota mediates the effect of host risk genes in Crohn’s disease

Crohn’s disease (CD) is a chronic inflammatory disease mainly characterized by chronic and relapsing intestinal inflammation. The pathogenesis of CD involves dysregulation of the immune response to commensal gut pro-inflammatory microbiota. Genome-wide association studies (GWAS) identified many genetic susceptibility loci associated with CD, such as NOD2, CARD9, ATG16L1, IRGM , and FUT2 , etc. These risk genes are associated with the relative abundance of particular bacteria. The combined risk score was found to be predictive of disease severity. Moreover, the exact composition of microbiota is known to determine host phenotypes, including metabolic and immunological phenotypes. In this study, we elucidated the association between host genetics, gut microbiota, and host phenotypes. We propose that the pathogenesis of Crohn’s disease is mediated by pro-inflammatory microbiota in genetically susceptible individuals.