Gut microbiota and metabolites are linked to disease progression in multiple sclerosis

Progressive multiple sclerosis is a neurological disease with few effective treatments and a poor understanding of the biological mechanisms associated with the transition from relapsing to progressive forms of the disease. Intestinal microbes and their metabolites have been reported to be altered in MS but little is known how these relate to disease progression. We investigated microbiota and metabolites in subjects with MS that remained stable vs. those that worsened and in subjects with relapsing MS that transitioned from relapsing to progressive disease over a two-year period. We found that Eubacterium hallii, Butyricoccaceae, Blautia, and other short-chain fatty acid-producing microbes had beneficial associations with measures of clinical and brain MRI worsening including disability scores, 3T MRI volumetric measures and cognitive and quality of life outcomes. Conversely, we found that Alistipes had detrimental associations with these measures. Global metabolomics identified serum and stool metabolites significantly altered in both subjects with progressive MS and in relapsing subjects that transitioned to progressive disease vs. healthy controls. Notably, the majority of fecal metabolites associated with disease progression were decreased, suggesting a deficiency of protective factors in the gut. In summary, using a unique MS cohort, our findings identify pathways by which the gut microbiome and its metabolites influence progressive MS.