The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease

作者：Fangyan Wang, Fanyu Qian, Qihao Zhang, Jian Zhao, Jianke Cen, Jiamin Zhang, Jinhui Zhou, Ming Luo, Chang Jia, Xing Rong, Maoping Chu · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1124118 · 被引用次数：45 · 研究领域：Diabetes and associated disorders、Gastroesophageal reflux and treatments、Infant Nutrition and Health

Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum ( C. butyricum ) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host’s inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate ...