Specific microbial ratio in the gut microbiome is associated with multiple sclerosis.

Abstract

Gut microbiota dysbiosis is associated with multiple sclerosis (MS), but the causal relationship between specific gut bacteria and MS pathogenesis remains poorly understood. Therefore, we profiled the stool microbiome of people with MS (PwMS) and healthy controls (HC) using shotgun metagenomic sequencing. PwMS showed a distinct microbiome compared to HC, with() andspecies as drivers of microbial communities in HC and PwMS, respectively. Administration of MS-drivingspecies () to mice resulted in increased levels of gut inflammatory markers and altered microbiota with increased capacity to induce proinflammatory cytokines. Utilizing experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we identified a lower guttoratio as a hallmark of the disease.-administered mice also showed a lowertoratio pre-EAE induction which correlated with increased disease severity post-EAE induction. The importance of thetoratio at the species level, lowerto(), was validated in our MS cohort and a large International Multiple Sclerosis Microbiome Study. Thus, our findings highlight theratio as a potential gut microbial marker in PwMS, opening avenues for microbiome-based diagnosis, prognosis, and therapy in MS.