Cholesterol-lowering effect of bile salt hydrolase from a<i>Lactobacillus johnsonii</i>strain mediated by FXR pathway regulation
Huanjing Zhu, Fang Zhao, Wenjun Zhang, Wenxu Xia, Ying Chen, Yanrong Liu, Zhiwen Fan, Yumeng Zhang, Yao Yang
Abstract
334 with high cholesterol reduction ability was selected to study the cholesterol-lowering mechanism mediated by farnesoid X receptor (FXR) regulation in mice. In the presence of recombinant BSH, mice had a larger bile acid pool. Analysis of individual bile acids revealed that bile acid composition was affected not only by recombinant BSH but also by the modulated gut microbiota. We confirmed a marked reduction in the transcription of FXR and its molecular targets in the ileum and a significant increase in the transcription of cholesterol 7a-hydroxylase (CYP7A1), which resulted in the increased bile acid synthesis and cholesterol-lowering effects. Notably, our work reveals the importance of BSH substrate specificity.