Human gut-derived commensal Prevotella histicola suppress experimental autoimmune encephalomyelitis in humanized mice

Our recent multiple sclerosis (MS) microbiome study indicates an important role of gut microbiota in pathogenesis of MS, an autoimmune disease of central nervous system. Gut microbiota help in maintaining immune-homeostasis by regulating balance between CD4 + CD25 + FoxP3 + regulatory T cells (Tregs) and pro-inflammatory Th1/Th17 cells. A shift of balance towards Th1/Th17 cells leading to inflammation and demyelination in central nervous system (CNS), is suggested to be responsible of disease initiation and/or relapses in MS. Therefore, gut commensals capable of restoring the microbiome to a healthy state could provide novel therapeutic options for treating autoimmune diseases including MS. Here, we report identification of human gut-derived commensal bacteria, Prevotella histicola (P. histicola) , which can suppress an autoimmune disease in HLA class-II transgenic model of experimental autoimmune encephalomyelitis (EAE), an experimental model of MS. P. histicola suppresses disease through modulation of systemic immune response. P. histicola challenge led to a decrease in pro-inflammatory Th1 (IFNγ) and Th17 (IL17) cytokines, and increase in the frequencies of CD4 + FoxP3 + Tregs, tolerogenic dendritic cells and suppressive macrophages. We also observed that mice with EAE had a altered gut microbiota compared to naive mice and treatment with P. histicola restored gut flora to a normal state which further support an important role of gut microbiota in EAE/MS. Our study provides compelling evidence that administration of gut commensals may regulate a systemic immune response and have a possible role in the treatment of autoimmune diseases.