Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation

Microbiome-based therapies are promising new treatment avenues. While global alterations in microbiota composition have been shown in multiple sclerosis, whether and how gut microbiota influence autoimmune responses in an antigen-specific manner is unclear. Here, we genetically engineered gut bacteria to express a brain antigen and dissect their pathogenic potential in a murine model of autoimmune neuroinflammation. Colonization with bacteria expressing myelin - but not ovalbumin-peptide exacerbates an encephalitogenic immune response in the gut by activating antigen-specific T cells as well as B cells leading to accelerated neuroinflammatory disease. These results demonstrate how antigen-specific microbial modulation can influence autoimmunity, providing insight for development of therapeutic strategies targeting specific bacterial taxa for treatment of MS and other autoimmune diseases.