Anti-diabetic effect of dicaffeoylquinic acids is associated with the modulation of gut microbiota and bile acid metabolism

作者：Yujie Huang, Weiqi Xu, Wei Dong, Guijie Chen, Yi Sun, Xiaoxiong Zeng · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.06.027 · 被引用次数：27 · 研究领域：Gut microbiota and health、Drug Transport and Resistance Mechanisms、Microbial Metabolites in Food Biotechnology

INTRODUCTION: The human gut microbiome plays a pivotal role in health and disease, notably through its interaction with bile acids (BAs). BAs, synthesized in the liver, undergo transformation by the gut microbiota upon excretion into the intestine, thus influencing host metabolism. However, the potential mechanisms of dicaffeoylquinic acids (DiCQAs) from Ilex kudingcha how to modulate lipid metabolism and inflammation via gut microbiota remain unclear. OBJECTIVES AND METHODS: The objectives of the present study were to investigate the regulating effects of DiCQAs on diabetes and the potential mechanisms of action. Two mice models were utilized to investigate the anti-diabetic effects of DiCQAs. Additionally, analysis of gut microbiota structure and functions was conducted concurrently with the examination of DiCQAs' impact on gut microbiota carrying the bile salt hydrolase (BSH) gene, as well as on the enterohepatic circulation of BAs and related signaling pathways. RESULTS: Our findings demonstrated that DiCQAs alleviated diabetic symptoms by modulating gut microbiota carrying the BSH gene. This modulation enhanced intestinal barrier integrity, increased enterohepatic circulation of conjugated BAs, and inhibited the farnesoid X receptor-fibroblast growth factor 15 (FGF15) signaling axis in the ileum. Consequently, the protein expression of hepatic FGFR4 fibroblast growth factor receptor 4 (FGFR4) decreased, accompanied by heightened BA synthesis, reduced hepatic BA stasis, a...