The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease.
The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease.
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DOI：
10.3389/fimmu.2023.1124118
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发表时间：
2023
影响因子：
7.3
通讯作者：
Chu, Maoping
中科院分区：
文献类型：
--
作者：
Wang, Fangyan;Qian, Fanyu;Zhang, Qihao;Zhao, Jian;Cen, Jianke;Zhang, Jiamin;Zhou, Jinhui;Luo, Ming;Jia, Chang;Rong, Xing;Chu, Maoping
川崎（Kawasaki disease，KD）是一种急性发热性全身性血管炎，在发达国家已成为获得性心脏病的主要病因。最近，在急性期KD患者中发现了肠道微生物群的改变。然而，对其特征和在KD发病机制中的作用知之甚少。在我们的研究中，在KD小鼠模型中证明了肠道微生物群组成的改变，其特征是产生SCFA的细菌减少。接下来，益生菌丁酸梭菌（C.丁酸）和抗生素混合物分别用于调节肠道微生物群。利用C.丁酸菌显著增加了产生SCFAs的细菌的丰度，减轻了冠状动脉病变，降低了炎症标志物IL-1β和IL-6，但抗生素消耗肠道细菌相反地恶化了炎症反应。KD小鼠肠道屏障蛋白Claudin-1、Jam-1、Occludin和ZO-1的减少以及血浆D-乳酸水平的增加证实了由微生态失调引起的肠道渗漏恶化宿主的炎症。机制上，SCFA，肠道微生物的主要有益代谢产物，以维持肠道屏障的完整性和抑制炎症，也被发现减少，特别是丁酸，乙酸和丙酸，在KD小鼠通过气相色谱-质谱（GC-MS）。此外，通过蛋白质印迹和RT-qPCR分析，KD小鼠中SCFAs转运蛋白、单羧酸转运蛋白1（MCT-1）和钠依赖性单羧酸转运蛋白1（SMCT-1）的表达也降低。正如预期的那样，口服C.丁酸治疗，但抗生素恶化。在体外，丁酸盐，而不是乙酸盐或丙酸盐，增加磷酸酶MKP-1的表达，使活化的JNK、ERK 1/2和p38 MAPK去磷酸化，对抗RAW 264.7巨噬细胞的过度炎症。这为益生菌及其代谢产物补充剂治疗KD提供了新的见解。
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 transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro, butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD.
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影响因子：
7.3
作者：
Kaneko, Kazunari;Akagawa, Shohei;Tsuji, Shoji
通讯作者：
Tsuji, Shoji
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影响因子：
12.2
作者：
Morrison DJ;Preston T
通讯作者：
Preston T
DOI：
10.1097/mpg.0b013e3182794432
发表时间：
2013-03-01
影响因子：
2.9
作者：
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通讯作者：
Glode, Mary P.
影响因子：
5.2
作者：
Kinumaki A;Sekizuka T;Hamada H;Kato K;Yamashita A;Kuroda M
通讯作者：
Kuroda M
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影响因子：
9
作者：
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通讯作者：
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