Gut microbiota-mediated ursodeoxycholic acids regulate the inflammation of microglia through TGR5 signaling after MCAO

被引：9
|
作者：
Zhang, Feng [1 ,3 ]
Deng, Yiting [2 ]
Wang, Huidi [1 ]
Fu, Jingxiang [1 ]
Wu, Guangyan [1 ]
Duan, Zhuo [1 ]
Zhang, Xiru [1 ]
Cai, Yijia [1 ]
Zhou, Hongwei [1 ,4 ,5 ]
Yin, Jia [2 ]
He, Yan [1 ,4 ,5 ,6 ]
机构：
[1] Southern Med Univ, Zhujiang Hosp, Microbiome Med Ctr, Dept Lab Med, Guangzhou 510282, Guangdong, Peoples R China
[2] Southern Med Univ, Nanfang Hosp, Dept Neurol, Guangzhou, Guangdong, Peoples R China
[3] Zhejiang Univ, Huzhou Cent Hosp, Dept Neurosurg, Sch Med, Huzhou, Peoples R China
[4] Guangdong Prov Clin Res Ctr Lab Med, Guangzhou 510033, Guangdong, Peoples R China
[5] Southern Med Univ, State Key Lab Organ Failure Res, Guangzhou 510515, Guangdong, Peoples R China
[6] Minist Educ, Key Lab Mental Hlth, Guangzhou 510515, Guangdong, Peoples R China
来源：
BRAIN BEHAVIOR AND IMMUNITY | 2024年 / 115卷
基金：
中国国家自然科学基金; 国家重点研发计划; 中国博士后科学基金;
关键词：
Ischemic stroke; Ursodeoxycholic acid; TGR5; NLRP3; inflammasome; Neuroinflammation; ISCHEMIC-STROKE; NEUROINFLAMMATION; GUIDELINES; RECEPTOR; OBESITY;
D O I：
10.1016/j.bbi.2023.11.021
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Ischemic stroke has been demonstrated to cause an imbalance of gut microbiota. However, the change in gut microbiota-mediated bile acids (BAs) metabolites remains unclear. Here, we observed a decrease in gut micro-biota-mediated BAs, especially ursodeoxycholic acid (UDCA), in the serum of stroke patients as well as in the intestine, serum and brain of stroke mice. Restoration of UDCA could decrease the area of infarction and improve the neurological function and cognitive function in mice in association with inhibition of NLRP3-related pro-inflammatory cytokines through TGR5/PKA pathway. Furthermore, knocking out TGR5 and inhibiting PKA activity reduce the protective effect of UDCA. Taken together, our results suggest that microbiota-mediated UDCA plays an important role in alleviating inflammatory responses and might be a promising therapeutic target in ischemic stroke.
引用
收藏
页码：667 / 679
页数：13
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