Abstract 331: Modulation Of Murine Vasculitis And Cardiovascular Inflammation By The Gut Microbiota

Abstract

Changes in intestinal microbiota composition and function are associated with development of cardiovascular disease, but the role of these alterations remains unclear in Kawasaki Disease (KD), an acute pediatric vasculitis that targets coronary arteries. Using a murine model of KD vasculitis, we observed reduced development of cardiovascular lesions in germ-free and antibiotic-treated mice. KD vasculitis in mice was associated with alterations in the gut microbiota composition and 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 propionate, both produced by A. muciniphila, or butyrate, produced by F. prausnitzii , reduced the development of vascular inflammation. Furthermore, treatment with Amuc_1100, a purified protein isolated from the outer membrane of A. muciniphila , decreased the severity of murine KD vasculitis. Beneficial effects of either pasteurized A. muciniphila or Amuc_1100 on murine KD vasculitis development were associated with improvement of gut barrier function. These results reveal an underappreciated gut microbiota-cardiovascular inflammation axis during murine KD vasculitis. Our findings may incite the development of novel diagnostic tools and therapeutic strategies that modulate the intestinal microbiota composition and function for KD patients.