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 <i>Prevotella copri</i> (<i>PC</i>) and <i>Blautia</i> species as drivers of microbial communities in HC and PwMS, respectively. Administration of MS-driving <i>Blautia</i> species (<i>Blautia wexlerae; BW</i>) 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 gut <i>Bifidobacterium</i> to <i>Akkermansia</i> ratio as a hallmark of the disease. <i>BW</i>-administered mice also showed a lower <i>Bifidobacterium</i> to <i>Akkermansia</i> ratio pre-EAE induction which correlated with increased disease severity post-EAE induction. The importance of the <i>Bifidobacterium</i> to <i>Akkermansia</i> ratio at the species level, lower <i>Bifidobacterium adolescentis</i> to <i>Akkermansia muciniphila</i> (<i>BA:AM</i>), was validated in our MS cohort and a large International Multiple Sclerosis Microbiome Study. Thus, our findings highlight the <i>BA:AM</i> ratio as a potential gut microbial marker in PwMS, opening avenues for microbiome-based diagnosis, prognosis, and therapy in MS.