压力通过CRH-CRHR1-线粒体通路触发肠道失调
Yiming Zhang1,2, Xiaoang Li1,2, Siqi Lu1,2
1Department of Gastroenterology, Peking University Third Hospital, Haidian District, Beijing, China.
NPJ biofilms and microbiomes
|September 30, 2024
概括
心理压力通过激活大脑-肠道通路来破坏肠道微生物群. 这一途径会损害结肠细胞线粒体,导致肠道失调,这是一种涉及胃肠道疾病的疾病.
科学领域:
- 神经胃肠病学 神经胃肠病学
- 微生物组研究 微生物组研究
- 细胞生物学 细胞生物学
背景情况:
- 压力影响大脑-肠轴障碍,如刺激性肠综合征 (IBS).
- 链接压力,大脑信号和肠道微生物群破坏的机制尚未完全理解.
- IBS患者表现出改变的肠道细菌和升高的压力激素.
研究的目的:
- 阐明大脑到肠道机制,通过这些机制,压力会诱导肠道失调.
- 确定皮质激素释放激素 (CRH) 途径在压力诱导的肠道改变中的作用.
- 探索与压力相关的胃肠道疾病的潜在治疗点.
主要方法:
- 对IBS患者和压力小鼠肠道微生物群组成的分析.
- 对血清CRH水平和结肠细胞线粒体超结构的评估.
- 研究CRH-CRH受体1型 (CRHR1) 信号通路及其下游影响 (cAMP/Ras/MAPK).
- 评估CRHR1对抗和线粒体呼吸增强的影响.
主要成果:
- IBS患者表现出增加的可选性厌氧和减少的义务性厌氧,与更高的CRH和缺陷线粒体相关.
- 在小鼠中,急性压力激活了CRH-CRHR1信号,损害了结肠细胞线粒体,并导致肠表皮缺氧.
- 这导致了紧张的小鼠显著的肠道失调.
- 阻断CRHR1或促进线粒体呼吸,保护免受压力诱导的损伤和失活性.
结论:
- 涉及CRH-CRHR1-线粒体通路的新型应激反应性脑至肠轴触发了肠道失调.
- 激活CRHR1通过cAMP/Ras/MAPK信号破坏结肠线粒体,导致肠道缺氧和失生症.
- 针对这种途径为压力诱导的胃肠道疾病提供了潜在的治疗策略.
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