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来自诺丽果富含酚类提取物干预小鼠供体的粪便微生物群移植通过以肠道微生物群依赖的方式调节FXR-FGF15途径改善脂质代谢紊乱。

Fecal Microbiota Transplantation from Noni Fruit Phenolic-Rich Extract Intervention Mouse Donors Ameliorates Lipid Metabolism Disorder by Regulating the FXR-FGF15 Pathway in a Gut Microbiota-Dependent Manner.

作者信息

Yang Derui, Yang Xiyuan, Zhou Yudie, Wang Huixian, Wang Ruimin

机构信息

School of Food Science and Engineering, Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Collaborative Innovation Center of One Health, Hainan University, Haikou 570228, China.

出版信息

J Agric Food Chem. 2025 Jul 16;73(28):17672-17684. doi: 10.1021/acs.jafc.5c05184. Epub 2025 Jun 27.

DOI:10.1021/acs.jafc.5c05184
PMID:40574570
Abstract

Noni fruit phenolic-rich extract (NFE) has been confirmed to alleviate lipid metabolism disturbance, with emerging evidence implicating bile acids (BAs) metabolism in a gut microbiota-dependent manner in mediating the effect. The effect and potential mechanism of fecal microbiota transplantation from NFE intervention mouse donors (FMT-NFE) on lipid metabolism disorder were investigated. The results reveal FMT-NFE intervention regulated the body weight, lipid profile levels, and liver damage. FMT-NFE intervention upgraded the abundance of bile salt hydrolase (BSH)-expressing bacteria and short-chain fatty acid (SCFA)-producing bacteria in feces, which is accompanied by changes of BSH activity and BAs profile as well as elevation of the SCFA level. Moreover, western blotting and immunofluorescence results confirmed the intestinal FXR-FGF15 pathway was activated by FMT-NFE intervention, which was accompanied by activation of the liver FXR and inhibition of CYP7A1 expression to control cholesterol-to-BAs conversion. These findings underscore the mechanisms behind maintaining BAs and lipid metabolism homeostasis of NFE.

摘要

诺丽果富含酚类提取物(NFE)已被证实可缓解脂质代谢紊乱,越来越多的证据表明胆汁酸(BAs)代谢以肠道微生物群依赖的方式介导了这一效应。研究了来自NFE干预小鼠供体的粪便微生物群移植(FMT-NFE)对脂质代谢紊乱的影响及潜在机制。结果显示,FMT-NFE干预可调节体重、脂质谱水平和肝脏损伤。FMT-NFE干预提高了粪便中表达胆汁盐水解酶(BSH)的细菌和产生短链脂肪酸(SCFA)的细菌的丰度,同时伴随着BSH活性和BAs谱的变化以及SCFA水平的升高。此外,蛋白质免疫印迹和免疫荧光结果证实,FMT-NFE干预激活了肠道FXR-FGF15通路,同时伴随着肝脏FXR的激活和CYP7A1表达的抑制,从而控制胆固醇向BAs的转化。这些发现强调了NFE维持BAs和脂质代谢稳态的机制。

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