由肠道微生物衍生的三甲基胺通过宿主受体TAAR5塑造昼夜节律
Kala K Mahen1,2,3, William J Massey2,4, Danny Orabi1
1Department of Cancer Biology, Cleveland Clinic, Cleveland, OH 44195, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
三甲基胺 (TMA) 是肠道微生物的代谢物,影响宿主的昼夜节律和代谢健康. 准TMA受体 (TAAR5) 揭示了与心脏代谢疾病相关的新的饮食-微生物-宿主相互作用.
科学领域:
- 微生物学 微生物学
- 代谢过程中的代谢.
- 时间生物学 时间生物学
背景情况:
- 来自肠道微生物的三甲基胺N-氧化物 (TMAO) 与心脏代谢疾病风险有关.
- 连接TMAO生产与人类疾病的机制尚不清楚.
- 饮食中的胆被肠道细菌转化为三甲基胺 (TMA),然后被宿主氧化为TMAO.
研究的目的:
- 调查主要代谢物TMA,而不是TMAO,是否影响宿主代谢恒温和昼夜节律.
- 探索宿主受体微氨基关联受体5 (TAAR5) 在调解TMA作用中的作用.
主要方法:
- 使用了缺乏TAAR5受体 (Taar5-/-) 的淘汰赛小鼠.
- 检查了在细菌TMA生产或宿主TMA氧化中遗传缺陷的小鼠.
- 评估基因表达,代谢荷尔蒙,肠道微生物组和行为中的昼夜节律.
主要成果:
- 缺少TAAR5的小鼠表现出基因表达,代谢荷尔蒙,肠道微生物组和行为中改变的昼夜节律.
- 细菌TMA生产或宿主TMA氧化中断也导致了改变的昼夜节律.
- 这些发现突出了TMA在调节昼夜生理学的作用.
结论:
- 肠道细菌对TMA的产生和通过TAAR5感知宿主与小鼠的昼夜节律的生理调节有关.
- 这些发现为与心脏代谢疾病相关的饮食-微生物-宿主相互作用提供了新的见解.
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