在衰老的肠道中微生物群/酸盐/FFAR3信号的异常会损害大脑功能
Sidharth P Mishra1,2,3, Shalini Jain1,2,3, Bo Wang4
1USF Center for Microbiome Research.
JCI insight
|February 8, 2024
概括
老化肠道微生物群通过减少丁酸盐导致炎症和认知能力下降. 恢复丁酸盐水平可以改善老年人的肠道和大脑健康.
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:
- 老龄化改变了肠道微生物群的组成,与认知和情绪障碍有关.
- 连接老化肠道微生物群与大脑功能障碍的机制尚不清楚.
研究的目的:
- 调查老化肠道微生物群和肠-大脑轴异常之间的因果关系.
- 确定丁酸盐及其受体在与年龄相关的认知和情绪缺陷中的作用.
主要方法:
- 从老年小鼠移植便微生物群到年轻小鼠.
- 评估肠道屏障完整性,炎症标志物和认知/焦虑行为.
- 对丁酸盐含量,粘素产生和自由脂肪酸受体2/3 (FFAR2/3) 表达的分析.
- 与丁酸盐的干预和FFAR2/3.3的基因操纵.
主要成果:
- 在年轻小鼠中,旧微生物种移植诱导了肠道炎症,漏肠和认知/焦虑问题.
- 在老化微生物群中观察到减少的酸盐生产和FFAR2/3信号.
- 丁酸盐的使用逆转了炎症和大脑功能障碍.
- 肠道特异性FFAR2/3损失模仿了与年龄相关的肠-大脑异常.
结论:
- 在老年肠道微生物群中减少的丁酸盐和FFAR2/3信号驱动肠道屏障功能障碍和大脑异常.
- 向酸盐-FFAR2/3通路为与年龄相关的肠-大脑轴衰退提供了一个治疗策略.
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