主体新陈代谢平衡了胆酸信号的微生物调节
Tae Hyung Won1,2, Mohammad Arifuzzaman3,4, Christopher N Parkhurst3
1Department of Chemistry and Chemical Biology, Boyce Thompson Institute, Cornell University, Ithaca, NY, USA.
Nature
|January 8, 2025
概括
肠道微生物群通过胆汁酸 (BA) 影响生理. 将BA转化为BA-甲基胺 (BA-MCY) 结合物的宿主修饰逆转了它们的功能,平衡了宿主和微生物的代谢途径.
科学领域:
- 微生物学
- 代谢学
- 生理学
背景情况:
- 肠道微生物代谢物,如胆酸 (BA),显著影响脊椎动物生理.
- 对于平衡微生物群衍生代谢物效应的精确宿主机制尚未完全理解.
研究的目的:
- 确定调节胆酸功能的宿主衍生代谢物.
- 研究素1 (VNN1) 在胆酸代谢中的作用.
- 阐明新型胆酸结合物的生理影响.
主要方法:
- 不针对小鼠组织的代谢学.
- 瓦宁1 (VNN1) 表达和功能的分析.
- 使用稳定同位素标记的BA-甲基胺 (BA-MCY) 结合物的体内研究.
- 超胆固醇和微生物群缺乏的小鼠模型.
- 便微生物移植和饮食干预 (胰岛素纤维).
主要成果:
- 在肠道中大量存在的依赖VNN1的BA-甲基胺 (BA-MCY) 结合物.
- 与自由BA不同的是,BA- MCYs作为法内索伊德X受体 (FXR) 抗剂,促进胆酸的产生.
- 在小鼠中,BA- MCY补充改善了高胆固醇.
- BA-MCY水平受到肠道微生物组成和食纤维的影响.
结论:
- 宿主依赖的BA-MCY结合是平衡宿主和微生物群代谢途径的关键机制.
- 在调节依赖FXR的生理和脂质代谢方面,BA- MCYs起着关键作用.
- 这些发现揭示了一种影响宿主代谢的新型宿主微生物群相互作用.
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