Gut microbiota modulates the development of murine Kawasaki disease vasculitis

Abstract

Abstract Alterations of gut microbiota composition and function influence the development of cardiovascular disease, but the role of these aberrations remains poorly understood in Kawasaki Disease (KD), an acute pediatric vasculitis that targets coronary arteries. Using a murine model of KD vasculitis, we found that germ-free and antibiotic-treated mice displayed reduced inflammation and cardiovascular lesions. Development of KD vasculitis in mice was associated with alterations in the composition of the intestinal microbiota, specifically decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Supplementation with live or pasteurized A. muciniphila or F. prausnitzii attenuated the severity of KD cardiovascular inflammation. Oral administration of the short-chain fatty acids acetate or butyrate, which are produced by A. muciniphila and F. prausnitzii respectively, or treatment with Amuc_1100, a purified protein isolated from the outer membrane of A. muciniphila, ameliorated the severity of KD cardiovascular lesions. Reduced development of KD vasculitis in mice receiving either pasteurized A. muciniphila or Amuc_1100 was associated with improvements of gut barrier function. These results reveal an underappreciated gut microbiota-cardiovascular inflammation axis during murine KD vasculitis. Our findings may stimulate the development of novel diagnostic tools and therapeutic strategies that modulate the intestinal microbiota composition and function for KD patients. Research is supported by the NIH grants R01AI072726 to M.A. and R01HL139766 to M.N.R.