由肠道微生物衍生而来的英多尔-3-氨酸改善了阿尔茨海默氏症患者的认知功能
Ling Li1, Mengzhen Jia1, Cong Yang1
1College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China.
Science advances
|November 28, 2025
概括
间歇性禁食 (IF) 可以通过改善认知和减少粉样蛋白斑块来帮助对抗阿尔茨海默病 (AD). 一个关键的微生物代谢物,-3-酸 (IPA),通过肠-大脑轴驱动这些好处.
科学领域:
- 神经科学是一个神经科学.
- 微生物学 微生物学
- 代谢学 代谢学 代谢学
背景情况:
- 阿尔茨海默病 (AD) 是一种进展性神经退行性疾病.
- 间歇性禁食 (IF) 在缓解AD病理方面表现有前途.
- 肠-大脑轴和微生物代谢物与神经退行有关.
研究的目的:
- 调查IF影响AD进展的机制.
- 为了确定参与IF神经保护作用的关键微生物代谢物.
- 探索这些代谢物对AD的治疗潜力.
主要方法:
- 使用AD转基因小鼠进行了16周的研究.
- 综合多基因组学 (基因组学,代谢学,微生物群分析).
- 药理学阻断神经元孕妇X受体 (PXR) 和微生物代谢物操纵.
- 对认知功能,粉样β (Aβ) 积累和神经炎症的评估.
- 对人类患者数据 (轻度认知障碍和AD) 的分析.
主要成果:
- 在小鼠中,IF改善了认知功能,并减少了Aβ积累.
- IF调节海马基因表达,肠道微生物群和血清代谢物.
- 印-3-酸 (IPA) 被确定为一种关键的代谢物,可以调解IF的作用.
- 阻止神经元PXR或IPA合成取消了IF的好处.
- 在人类患者中观察到较低的IPA水平,这些患者有轻度认知障碍和AD.
- IPA补充剂和IPA产生细菌的管理复制了IF的认知益处.
- IPA表现出抗炎活性,并减少了Aβ在大脑中的积累.
结论:
- 间歇性禁食对抗阿尔茨海默病具有神经保护作用.
- 肠道微生物代谢物英多尔-3-酸 (IPA) 是IF益处的关键媒介.
- 针对IPA和肠-大脑轴是一个有前途的治疗策略.
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