Abstract 52: The Gut Microbiome Alters Susceptibility to Coronary Inflammation in Kawasaki Disease

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Abstract

The gut microbiome has been shown to have immunomodulatory capabilities, and changes in the composition of the microbiome have altered the pathogenesis of inflammatory diseases. In this study, we sought to investigate the effects of the microbiome on the pathogenesis of Kawasaki Disease (KD) using the Lactobacillus cell wall extract (LCWE)-induced coronary arteritis model. Using qPCR on mouse fecal samples, we quantified bacterial communities through the 16S rRNA gene. Animals originating from the same supplier where housed in two independent facilities. There were marked elevations in Bacteroides, Bifidobacteria, Lactobacillus and segmented filamentous bacteria (SFB) and decrease in Clostridia in Facility A compared to Facility B. The transition to the newer Facility B resulted in a reduction in disease induction by LCWE to 26% (25/95), compared to 50% (35/70) at Facility A.

Addition of antibiotics to the drinking water to deplete the microbiome reduced disease incidence to 40% (2/5) of mice housed at Facility A compared to 100% (5/5) of untreated mice, suggesting that components of the microbiome are necessary to exacerbate inflammation. To address whether the gut microbiome was sufficient to support disease susceptibility, the cecal contents of the susceptible mice at A were gavaged into the less susceptible mice at B. Recipients of the cecal contents from Facility A had an increased disease incidence of 91% (10/11) compared to 60% (6/10) in control mice which received cecal contents from mice housed in Facility B.

We also report elevated levels of IL-17 in the serum of SFB-colonized mice. SFB, known to exacerbate several models of autoimmunity, was completely absent in mice housed at Facility B. Interestingly Th17 and its associated cytokine IL-17 have been associated with acute KD, but its role in pathogenesis remains unclear. Th17 cells have been implicated in autoimmunity, and are also important players in gut homeostasis. Our data provide evidence for the role of the gut microbiome in modulating the immunopathogenesis of KD, pointing to the important interactions of commensal and pathogenic factors as determinants of disease.

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