Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota
Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota
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DOI：
10.3389/fimmu.2020.01616
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发表时间：
2020-07-24
影响因子：
7.3
通讯作者：
Tsuji, Shoji
中科院分区：
文献类型：
--
作者：
Kaneko, Kazunari;Akagawa, Shohei;Tsuji, Shoji
川崎病（KD）由Tomisaku川崎博士于1967年首次描述。KD的病因已被全面研究，但仍在很大程度上未知。该疾病似乎是由于遗传和环境易感性因素与感染性触发因素的相互作用，随后是以急性期炎性细胞因子和趋化因子水平升高为特征的随后异常免疫应答。越来越多的证据表明，辅助性T细胞17（Th 17）和调节性T细胞（T细胞）之间的不平衡与KD的异常免疫应答有关。用于检测和鉴定肠道细菌的非培养技术的最新进展使得能够发现Th 17和Treg分化受肠道微生物群产生的短链脂肪酸（SCFA）（特别是丁酸盐）调节。这一发现提供了生态失调（定义为肠道微生物群组成的变化）与各种炎症性疾病之间的机制联系。在此基础上，我们提出，生态失调，减少生产的SCFAs，导致失衡的Th 17/THBG，可能参与KD的病因。一项初步研究支持了这一假设，因为在SCFA中，KD患者中仅丁酸盐的粪便浓度显著降低。这种不断发展的观点促使我们对来自诊断时未接受过免疫治疗的KD患者粪便的细菌DNA进行宏基因组分析。同时测量外周血中的Th 17 s/T细胞亚群和粪便中的SCFA浓度将提供有关KD中生态失调和免疫应答失调之间相关性的有价值信息。
Kawasaki disease (KD) was first described by Dr. Tomisaku Kawasaki in 1967. The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Evidence has mounted to suggest that an imbalance between T helper 17 cells (Th17s) and regulatory T cells (Tregs) is associated with aberrant immune responses in KD. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This finding provided a mechanistic link between dysbiosis, defined as changes in the composition of the gut microbiota, and various inflammatory diseases. On this basis, we propose that dysbiosis, with reduced production of SCFAs leading to imbalances of Th17s/Tregs, could be involved in the etiology of KD. A pilot study supported this hypothesis, as only fecal concentrations of butyrate were significantly reduced in KD patients among SCFAs. This evolving perspective prompted us to undertake metagenomic analyses of bacterial DNA from the feces of KD patients who were antibiotic-naive at diagnosis. Simultaneous measurements of Th17s/Tregs in peripheral blood and SCFA concentrations in feces would provide valuable information regarding the association between dysbiosis and dysregulated immune responses in KD.