Microbiota-produced immune regulatory bile acid metabolites control central nervous system autoimmunity

regulatory T (Treg) cell differentiation at the expense of Th17 cells. Here, we show that bacteria releasing enzymes responsible for secondary BAMs production are under-represented in the gut of MS patients, resulting in significantly reduced intestinal concentration of DCA and immune dysregulation with increased percentage of Th17 cells. We validated our human findings in a preclinical model of MS by showing that DCA/LCA administration prevents experimental autoimmune encephalomyelitis (EAE) by dampening Th17 cell differentiation and the effector phenotype of myelin-reactive T cells. Our data highlight the key role of immune regulatory BAMs for the prevention of central nervous system (CNS) autoimmunity.