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 may aid in developing microbiome-based applications; however, these interactions remain unclear. Here, we aimed to elucidate how Veillonella ratti MHL0042, isolated from human infant feces, modulates neuroinflammation and disease severity in experimental autoimmune encephalomyelitis, a murine MS model. Whole metagenomic sequencing revealed that V. ratti MHL0042 reshaped disrupted gut microbiota via microbial interactions throughout the intestinal tract. V. ratti MHL0042 administration significantly reduced central nervous system inflammation, notably decreasing CD4+IFN-γ⁺ T cell populations and activated spinal cord microglia. Mechanistically, V. ratti MHL0042 depleted pldA-containing bacteria, involved in phosphatidylethanolamine metabolism, thus elevating dioleoyl phosphatidylethanolamine (DOPE) levels. Increased DOPE was not only detected in the intestinal tract but also extended systemically and reflected in the central nervous system. Exogenous DOPE administration recapitulated the attenuation of experimental autoimmune encephalomyelitis pathogenesis by suppressing microglial activation. These findings highlight the therapeutic applicability of the microbiome and underscore its potential in human disease treatment.