饮食中获得的乌罗素A是由人类肠道Enterocloster物种编码的脱酶生成的
Reilly Pidgeon1, Sacha Mitchell1, Michael Shamash2
1Department of Pharmacology & Therapeutics, McGill University, 3655 Prom. Sir-William-Osler, Montreal, Quebec, H3G 1Y6, Canada.
Nature communications
|January 24, 2025
概括
研究人员确定了Enterocloster物种中的uroc dehydroxylase (ucd) 操作子,该操作子对于从食化合物中产生urolithin A (uroA) 至关重要. 这一发现解释了肠道微生物群对uroA代谢的个体差异.
科学领域:
- 微生物学 微生物学
- 代谢学 代谢学 代谢学
- 肠道微生物组研究研究
背景情况:
- 乌罗立A (uroA) 是一种有益的多,由肠道细菌从食中的ellagitannins产生的.
- 它的生产机制,特别是uroC的脱化,仍然在很大程度上是未知的.
- UroA通过线粒细胞衰变,基碳化合物受体信号传递和免疫功能影响宿主健康.
研究的目的:
- 阐明负责 uroC 脱化为 uroA 的分子机制.
- 为了确定特定的细菌物种和基因参与uroA生产.
- 了解人类肠道微生物群中的 uroA 生产通路的流行和活性.
主要方法:
- 利用未定位的细菌转录组学,蛋白组学和比较基因组学.
- 在Enterocloster物种中识别和特征 uroC脱酶 (ucd) 操作子.
- 分析了人类转基因组学数据集,并进行了ex vivo人类便化.
主要成果:
- 在Enterocloster物种中发现一种可诱导的ucd操作子,该操作子编码了一种依赖于molybdopterin的酶复合体.
- 证明这个复合物在9-OH位置特异性地将uroC脱化为uroA.
- 证实了 uroC-代谢的Enterocloster物种和ucd operon基因在人类便中的流行.
- 在便样本中的ucd基因转录与uroA生产之间显示了直接的相关性.
结论:
- 肠道体物种和ucd操作子是人类尿素A生产的关键参与者.
- 该ucd操作子的活性解释了urolithin代谢的个体间变异性.
- 这项研究为研究微生物多代谢提供了一个多学科的框架.
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