Aberrant activation of Th17 cells by the gut microbiota contributes to autoimmune and chronic inflammatory disease; however, the mechanisms responsible and their diet-dependence remain unclear. Here, we show that the disease-associated gut Actinobacterium Eggerthella lenta increases intestinal Th17 cells and worsens colitis. E. lenta-induced disease and Th17 accumulation was Rorc-dependent and strain variable. Comparative genomics revealed a single genomic locus predictive of Th17 accumulation

more »

... nd a gene within this locus, encoding the Cgr2 enzyme, was sufficient to increase Th17 cells. Increased dietary arginine prevented E. lenta mediated Th17 accumulation and ameliorated colitis suggesting that diet can modulate microbial associated disease. These results expand the mechanisms through which bacteria shape mucosal immunity and demonstrate the feasibility of identifying the causal species, genes, and enzymes that contribute to autoimmune disease.