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, United States.
eLife
|January 29, 2026
概括
三甲基胺 (TMA) 是肠道微生物的代谢物,通过激活宿主受体TAAR5.5来破坏昼夜节律和代谢平衡. 这揭示了一种新的饮食-微生物-宿主相互作用,影响心脏代谢疾病风险.
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:
- 高水平的三甲基胺N氧化物 (TMAO) 将肠道微生物与心脏代谢疾病联系起来.
- 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TMA,前体代谢物是否影响宿主代谢平衡和昼夜节律.
- 确定微量胺相关受体5 (TAAR5) 在调解TMA作用中的作用.
- 探索TMA生产/氧化和昼夜节律调节之间的联系.
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,荷尔蒙,微生物组和行为中改变的昼夜节律.
- 细菌TMA产生的遗传缺失或宿主TMA氧化也导致了改变的昼夜节律.
- 这些发现表明TMA和TAAR5与昼夜节律的生理调节有关.
结论:
- 肠道细菌代谢物TMA由宿主受体TAAR5感知,在调节宿主昼夜节律方面发挥着重要作用.
- 这一途径代表了一种与心脏代谢健康相关的新型饮食-微生物-宿主相互作用.
- 了解TMA的作用为代谢和生理节律障碍提供了新的治疗点.
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