与年龄相关的微生物组代谢物改变了RNA剪接和大脑中的染色质可访问性
Meenakshi Chakraborty1, Sophia M Shi2,3,4,5, Imani E Porter1
1Department of Genetics, Stanford University, Stanford, CA, USA.
bioRxiv : the preprint server for biology
|November 19, 2025
概括
研究人员确定了肠道微生物群代谢物,影响大脑衰老和神经退行. 他们发现三甲基胺N-氧化物 (TMAO) 恶化神经退行,而甘氨酸 (GDCA) 通过调节基因表达来保护大脑.
科学领域:
- 微生物学 微生物学
- 神经科学是一个神经科学.
- 代谢学 代谢学 代谢学
背景情况:
- 肠道微生物组产生代谢物,影响宿主生物学,包括大脑功能.
- 需要一个系统的方法来识别和验证肠-大脑信号分子.
研究的目的:
- 为了确定微生物组衍生代谢物随着年龄的增长而变化,并影响小鼠大脑.
- 了解神经退行过程中这些代谢物的分子机制.
主要方法:
- 对大规模人类代谢学数据集 (n ≥1200) 的分析.
- 在体外转录性查代谢产物.
- 在体内小鼠模型与多原子分析.
主要成果:
- 确定了30种与年龄相关的微生物组代谢物;三甲基胺N氧化物 (TMAO) 加剧神经退行,影响线粒体功能,糖解和RNA剪接.
- 甘氨酸 (GDCA) 调节染色质的可访问性,抑制保护基因,并降低运动能力.
结论:
- 一个可扩展的框架将微生物组代谢物与宿主病理联系起来.
- 确定了诱导与神经退行相关的分子变化的特定微生物代谢物.
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