由肠道微生物组产生的胆汁酸代谢物延长了宿主肠道细胞中的循环周期
bioRxiv : the preprint server for biology
|March 31, 2025
概括
肠道微生物影响宿主的昼夜节律. 研究人员发现,胆汁酸代谢产物石化酸 (LCA) 通过稳定核心时钟蛋白来延长昼夜周期,将饮食,微生物和身体时钟联系起来.
科学领域:
- 微生物学 微生物学
- 时间生物学 时间生物学
- 代谢学 代谢学 代谢学
背景情况:
- 主体的昼夜信号,食模式和肠道微生物组之间有着复杂的联系.
- 调解这些连接的分子机制和特定的微生物代谢物尚未得到充分理解.
研究的目的:
- 为了确定影响宿主昼夜信号的肠道微生物代谢物.
- 阐明这些代谢物影响昼夜钟的分子途径.
主要方法:
- 肠道微生物代谢物的图书馆的表型选.
- 评估石灰酸 (LCA) 对人类结肠细胞内核钟基因转录的影响.
- 研究LCA对氨酸激酶1 δ/ε (CK1δ/ε) -蛋白酸酶1 (PP1) 反循环和加密染色体2 (CRY2) 稳定性的影响.
- 分析LCA在食后对小鼠大肠和大肠的昼夜转录的影响.
主要成果:
- 胆汁酸代谢产物石化酸 (LCA) 被确定为一个昼夜调节器.
- 以剂量为依赖的LCA延长了人类结肠细胞中hPer2基因转录的昼夜周期.
- 已经证明LCA可以调节CK1δ/ε-PP1反循环并稳定CRY2蛋白.
- 在小鼠的远端大肠和大肠中,LCA的使用改变了昼夜转录模式.
结论:
- 石化酸 (LCA) 作为一个分子链接,将宿主昼夜生物与肠道微生物组连接起来.
- 在调节昼夜节律方面,LCA的作用为食物诱导的振荡器提供了机械的洞察力.
- 研究结果表明,通过准LCA介导的途径来调节宿主健康的潜在治疗途径,考虑到昼夜节律,食和代谢疾病之间的联系.
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