Jena Prasant K, Wakita Daiko, Gomez Angela C, Carvalho Thacyana T, Atici Asli E, Aubuchon Emily, Narayanan Meena, Lee Youngho, Fishbein Michael C, Takasato Yoshihiro, Kurashima Yosuke, Kiyono Hiroshi, Cani Patrice D, de Vos Willem M, Underhill David M, Devkota Suzanne, Chen Shuang, Shimada Kenichi, Crother Timothy R, Arditi Moshe, Noval Rivas Magali
Division of Infectious Diseases and Immunology, Department of Pediatrics, Guerin Children's at Cedars-Sinai Medical Center, Los Angeles, CA (P.K.J., D.W., A.C.G., T.T.C., A.E.A., E.A., M.N., Y.L., S.C., K.S., T.R.C., M.A., M.N.R.).
Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center, (P.K.J., D.W., A.C.G., T.T.C., A.E.A., E.A., M.N., Y.L., S.C., K.S., T.R.C., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA.
Circ Res. 2025 Apr 11;136(8):e53-e72. doi: 10.1161/CIRCRESAHA.124.325079. Epub 2025 Mar 3.
Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear.
We used the cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from , and their impact on vasculitis development was assessed.
We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of and . 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 also reduced the severity of vascular inflammation.
This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD 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.
肠道微生物群的改变有助于多种心血管疾病的发病机制，但它们如何影响川崎病（KD）这种急性儿童血管炎的发展仍不清楚。
我们使用KD血管炎的细胞壁提取物（LCWE）小鼠模型来评估肠道微生物群对血管炎症发展的作用。我们评估了微生物群耗竭小鼠中血管炎的严重程度。使用16S rRNA基因测序来表征注射LCWE小鼠的粪便微生物组组成。一些小鼠组口服选定的活细菌或巴氏杀菌细菌、短链脂肪酸或来自[具体来源未提及]的Toll样受体2信号外膜蛋白Amuc_1100，并评估它们对血管炎发展的影响。
我们报告称，在模拟KD血管炎的小鼠模型中，耗尽肠道微生物群可减少心血管炎症的发展。心血管病变的发展与肠道微生物群组成的改变有关，特别是[具体细菌名称未提及]和[具体细菌名称未提及]的丰度降低。口服补充这些活细菌或巴氏杀菌单个细菌中的任何一种或它们产生的短链脂肪酸可减轻心血管炎症，局部免疫细胞浸润减少即反映了这一点。用Amuc_1100治疗也降低了血管炎症的严重程度。
本研究揭示了KD血管炎发病机制中一个未被充分认识的肠道微生物群 - 心血管炎症轴，并确定了特定的肠道共生菌，它们通过产生代谢产物或通过能够增强和支持肠道屏障功能的细胞外蛋白来调节小鼠的血管炎。
