Gut microbiome modulation by Veillonella ratti induces resistance to EAE pathogenesis via microbe-derived metabolites

The progression of multiple sclerosis (MS) is potentially influenced by the microbiome. Elucidating host-microbiome interactions in MS could aid in developing microbiome-based applications; however, these interactions remain unclear. Here, we aimed to elucidate how human infant feces-derived Veillonella ratti MHL0042 modulates neuroinflammation and disease severity in experimental autoimmune encephalomyelitis (EAE), a murine MS model. Whole metagenomic sequencing revealed that V. ratti MHL0042 modulated the disrupted gut microbiota via microbial interactions throughout the intestinal tract. V. ratti MHL0042 administration significantly reduced central nervous system inflammation, notably decreasing CD4+IFN-?? T cell populations and activated spinal cord microglia. Mechanistically, V. ratti MHL0042 depleted pldA-containing bacteria, involved in phosphatidylethanolamine metabolism, thus elevating dioleoylphosphatidylethanolamine (DOPE) levels, as determined via metabolomic analysis. Exogenous DOPE administration recapitulated the attenuation of EAE pathogenesis by suppressing microglial activation. These findings highlight the therapeutic applicability of the microbiome and underscore its future potential in human disease treatment