Intestinal Microbiota Contributes to the Development of Cardiovascular Inflammation and Vasculitis in Mice

BACKGROUND: Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease, an acute pediatric vasculitis, remains unclear. Here, using a murine model mimicking Kawasaki disease vasculitis, we assessed the contribution of the intestinal microbiota to the development of vascular inflammation. METHODS AND RESULTS: We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking Kawasaki disease vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii . Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100, the TLR-2 signaling outer membrane protein from Akkermansia muciniphila , also reduced the severity of vascular inflammation. CONCLUSIONS: This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in Kawasaki disease vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.