肠道微生物加剧了神经疾病中的全身炎症和行为障碍CADASIL
Sheng Liu1, Xuejiao Men2, Yang Guo1
1Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China.
Microbiome
|September 8, 2023
概括
这项研究表明,肠道微生物组的改变,神经递质失衡和细胞因子的升高与带有皮下心脏病发作和白细胞大脑病变 (CADASIL) 的脑自体主导动脉病相关,影响疾病预测.
科学领域:
- 神经科学是一个神经科学.
- 微生物学 微生物学
- 遗传学 遗传学 是一个
背景情况:
- 大脑自体主导性动脉病变与皮下心脏病发作和白脑病变 (CADASIL) 是一种与NOTCH3突变相关的遗传小血管疾病.
- 环境因素,包括肠道微生物群,可能会影响CADASIL的临床表现.
研究的目的:
- 与健康对照组相比,研究CADASIL患者的肠道微生物组,代谢组,神经递质和细胞因子.
- 探索与CADASIL病理学的综合病理学关联,并确定潜在的生物标志物.
主要方法:
- 便转基因组,便和血清代谢组,神经递质和细胞因子分析在24名CADASIL患者和28名对照组中进行.
- 在小鼠模型中采用了集成的奥米克分析,随机森林分类和向的文化奥米克.
主要成果:
- 卡达西尔患者表现出肠道微生物群的组成和功能发生变化,对辅酶A,胺和黄素的合成途径减弱.
- 观察到神经递质平衡受损 (谷氨酸/GABA比率) 和炎症性细胞因子升高,与特定的细菌物种如Fusobacterium varium相关.
- 一个随机森林模型整合了微生物物种,细胞因子和神经递质,实现了高CADASIL预测性 (AUC=0.89).
结论:
- 研究结果表明,大脑-肠-微生物轴与CADASIL之间存在显著联系.
- 来自患者的F. varium诱导了小鼠的炎症和行为变化,表明疾病机制中的潜在因果作用.
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