The study investigates the role of gut microbiota in the induction and severity of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Mice maintained under germ-free conditions develop significantly attenuated EAE compared to conventionally colonized mice. Germ-free animals produce lower levels of proinflammatory cytokines IFN-γ and IL-17A in the intestine and spinal cord but display increased levels of regulatory T cells (Tregs). Mechanistically, gut dendritic cells from germ-free animals are less effective in stimulating proinflammatory T cell responses. Intestinal colonization with segmented filamentous bacteria (SFBs) promotes IL-17 production in the gut and induces IL-17A-producing CD4+ T cells (Th17) in the CNS. Notably, germ-free animals harboring SFBs alone develop EAE, indicating that gut bacteria can affect neurological inflammation. These findings suggest that the intestinal microbiota profoundly impacts the balance between pro- and anti-inflammatory immune responses during EAE and highlight the potential therapeutic targets for extraintestinal inflammatory diseases like MS.The study investigates the role of gut microbiota in the induction and severity of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Mice maintained under germ-free conditions develop significantly attenuated EAE compared to conventionally colonized mice. Germ-free animals produce lower levels of proinflammatory cytokines IFN-γ and IL-17A in the intestine and spinal cord but display increased levels of regulatory T cells (Tregs). Mechanistically, gut dendritic cells from germ-free animals are less effective in stimulating proinflammatory T cell responses. Intestinal colonization with segmented filamentous bacteria (SFBs) promotes IL-17 production in the gut and induces IL-17A-producing CD4+ T cells (Th17) in the CNS. Notably, germ-free animals harboring SFBs alone develop EAE, indicating that gut bacteria can affect neurological inflammation. These findings suggest that the intestinal microbiota profoundly impacts the balance between pro- and anti-inflammatory immune responses during EAE and highlight the potential therapeutic targets for extraintestinal inflammatory diseases like MS.