Human gut commensal Prevotella histicola ameliorates disease as efficiently as Copaxone and Interferon-β in a preclinical animal model of multiple sclerosis

Abstract

Abstract Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. We and others have shown that gut microbiota play an important role in disease pathogenesis of MS as there is an enrichment or depletion of specific gut bacteria compared to healthy controls (HC). Thus the specific human gut bacteria found depleted or showing lower abundance in MS patients can be used as potential drug to treat MS. Further, we and others have shown that patients with MS have either lower abundance of Prevotella compared to HC or an increased level of Prevotella in patients receiving disease modifying therapies such as Copaxone and/or Interferon beta (IFN-β). We have previously identified a specific strain Prevotella histicola within Prevotella genus which can suppress disease in experimental autoimmune encephalomyelitis (EAE) animal model of MS. In this present study we compared disease suppressing ability of P. histicola to Copaxone or IFN-β in HLA-DR3.DQ8 transgenic mouse model of MS. We observed that P. histicola suppresses EAE as efficiently as Copaxone and IFN-β. P. histicola treated mice showed higher level of CD4+FoxP3+ regulatory T cell frequencies and decreased levels of pro-inflammatory cytokines IFNγ and IL17 suggesting that P. histicola suppresses disease through immunomodulation. Fecal microbiota analysis of different groups showed that group receiving Prevotella histicola had a distinct gut microbiota than the control group suggesting that P. histicola as might suppresses disease through modulation of gut microbiota. In conclusion, our study suggests that human gut commensal Prevotella histicola can provide an alternate treatment option for MS patients.