在肝硬化中,肠-大脑轴是肝脑病的基础
Xiaolong He1, Mengyao Hu1, Yi Xu1
1Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Nature medicine
|January 8, 2025
概括
肠道细菌氨脱酶 (PDC) 和其产物乙胺 (PEA) 导致肝硬化中的肝脑病变 (HE). 针对PDC或PEA显示出治疗HE和预测其风险的希望.
科学领域:
- 微生物学 微生物学
- 神经科学是一个神经科学.
- 胃肠病学 胃肠病学
背景情况:
- 肝发性脑病变 (HE) 影响50-70%的肝硬化患者,与肠道失调有关.
- 连接肠道微生物群与HE病变的确切机制尚不清楚.
研究的目的:
- 研究细菌神经毒素在肝硬化相关的HE中所起的作用.
- 确定对高等教育的潜在治疗和预测目标.
主要方法:
- 使用元基因组数据构建的肠-大脑模块来评估细菌神经毒素.
- 利用了无细菌的肝硬化小鼠模型,这些小鼠被Ruminococcus gnavus.
- 从HE患者移植便微生物群给小鼠.
- 测量了氨酸脱碳酶 (PDC) 基因表达和乙胺 (PEA) 水平.
- 评估了单胺氧化酶-B活性和神经症状.
主要成果:
- 主要来自Ruminococcus gnavus的PDC基因在肝硬化患者中增加了十倍,特别是在HE患者中.
- 在肝硬化小鼠中的R. gnavus殖民诱导大脑PEA积累,记忆障碍,震和神经元损失.
- PEA积累是由于肝脏和血清中单氨酸氧化酶-B活性下降造成的.
- 准PDC或PEA在小鼠中逆转了神经症状.
- 来自HE患者的便微生物群移植在小鼠中复制了HE症状.
- 高基线PEA水平预测了HE术后手术的风险增加7倍.
结论:
- 增加的Ruminococcus gnavus和随后的乙烯胺生产有助于HE的病变.
- 针对PDC-PEA途径为高等教育提供了一个有前途的治疗策略.
- 甲胺水平可以作为HE风险的预测生物标志物.
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