Spontaneous Translocation of a Gut Pathobiont Drives Autoimmunity

Despite multiple associations between the microbiota and immune diseases, its role in autoimmunity is poorly understood. Here, we show that a gut pathobiont, E. gallinarum, translocates to tissues including the liver in a spontaneous model of autoimmunity. A single antibiotic that prevents mortality in this model, suppressed growth of E. gallinarum in tissues, pathogenic autoantibodies and T cells. Hepatocyte-commensal cocultures demonstrated induction of autoimmune-promoting factors. Translocation in monocolonized and autoimmune-prone mice induced autoantibodies and mortality that could be prevented with an intramuscular vaccine targeting this pathobiont. E. gallinarum-specific DNA could be recovered from liver biopsies of autoimmune patients, suggesting similar processes in humans. Collectively, these data indicate that a human pathobiont translocates spontaneously to promote autoimmunity in genetically predisposed hosts, broadening our understanding of autoimmune host-microbiota interactions.