Interactions Between Host Genetics and the Gut Microbiome in CNS Autoimmunity

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Project Summary Multiple sclerosis (MS) is a devastating autoimmune neuroinflammatory disease with a strikingly increasing incidence world-wide, implicating the influence of environmental factors. While genetics of MS are beginning to be understood, they can account for at most ~30% of the disease risk. The remainder of the disease risk is accounted for by environmental factors and gene-by-environment (G×E) interactions. Mechanisms of G×E in MS are not well understood, and are difficult to study in humans. Mounting evidence implicates a novel environmental risk factor for MS: dysregulation of the gut microbiome. In this application, we propose to take a genome-wide approach to identify gene × microbiome interactions in a novel and powerful mouse genetics system. These studies cannot be carried out in humans, and they will provide important mechanistic understanding of G×E in autoimmune disease of the CNS, and deliver cause vs. effect distinctions that are lacking in epidemiologic studies.