Bifidobacterium pseudolongum-Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP-PKG-mTORC1 Pathway

文献类型： 外文期刊

第一作者： Zhang, Ke

作者： Zhang, Ke;Xu, Yangbin;Zheng, Yining;Zhang, Ting;Yan, Yiting;Lei, Yu;Cao, Xi;Wang, Xiaolong;Chen, Yulin;Deng, Lu;Yang, Yuxin;Wu, Yujiang;Yan, Frances;Lei, Zhaomin;Brugger, Daniel

作者机构：

关键词： 12-ketodeoxycholic acid; bile acid; gut microbiota; inflammatory bowel disease; mTOR

期刊名称：ADVANCED SCIENCE （ 影响因子：14.1； 五年影响因子：15.6 ）

ISSN：

年卷期： 2024 年 11 卷 43 期

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收录情况： SCI

摘要： Carvacrol and thymol (CAT) have been widely recognized for their antimicrobial and anti-inflammatory properties, yet their specific effects on colitis and the mechanisms involved remain insufficiently understood. This study establishes a causative link between CAT administration and colitis mitigation, primarily through the enhancement of Bifidobacterium pseudolongum abundance in the colon. This increase promotes the production of secondary bile acids, particularly hyodeoxycholic acid (HDCA) and 12-ketodeoxycholic acid (12-KCAC), which exert anti-inflammatory effects. Notably, CAT does not alleviate colitis symptoms in germ-free mice, indicating the necessity of gut microbiota. This research uncovers a novel regulatory mechanism where HDCA and 12-KCAC inhibit colonic inflammation by reducing the expression of transmembrane guanylate cyclase 1A in the colonic epithelium. This downregulation elevates intracellular Ca2+ and cGMP levels, activating protein kinase G (PKG). Activated PKG subsequently suppresses the mTOR signaling pathway, thereby ameliorating dextran sulfate sodium (DSS)-induced colonic damage. These findings highlight potential metabolites and therapeutic targets for preventing and treating colitis. Bifidobacterium pseudolongum, HDCA, and 12-KCAC emerge as promising candidates for therapeutic interventions in colitis and related disorders characterized by impaired tight junction function.

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