连接肠道微生物群和零星克鲁茨菲尔特-雅各布病的介质:孟德尔的随机化研究
Jie Shao1, Tengfei Su2, Jinyan Wang3
1Department of Neurology, The First Hospital of Jilin University, Changchun, China. shaojie1994@jlu.edu.cn.
AMB Express
|August 18, 2025
概括
肠道细菌影响偶尔的克鲁茨菲尔特-雅各布病 (sCJD) 风险,一些微生物提供保护,而另一些微生物则构成威胁. 鉴定出S-甲基半氨酸是致病途径的关键调解者,提供了新的治疗点.
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 是一个遗传学.
背景情况:
- 肠道微生物组在零星克鲁茨菲尔特-雅各布病 (sCJD) 中的作用是公认的,但因果关系和脑脊液 (CSF) 代谢物的参与尚未完全理解.
- 现有的研究缺乏确立的机制,将肠道微生物组成与sCJD病原和进展联系起来.
研究的目的:
- 调查肠道微生物群组成和发展偶发克鲁茨菲尔特-雅各布病 (sCJD) 的风险之间的因果关系.
- 探索大脑脊髓液 (CSF) 代谢物在肠道微生物组-sCJD轴中的调解作用.
- 确定潜在的微生物生物标志物用于sCJD风险分层和治疗点.
主要方法:
- 利用双向门德尔随机化 (MR) 分析,整合全基因组关联研究 (GWAS) 总结统计.
- 包括关于肠道微生物群组成的数据 (FINRISK 2002队列,n=5,959),CSF代谢物 (威斯康星州ADRC和WRPC,n=291),以及sCJD病例和对照 (5208 vs. 511,675).
- 采用调解分析来评估S-甲基半氨酸在特定微生物种类和sCJD风险之间的途径中的作用.
主要成果:
- 确定了五种与sCJD风险相关的微生物种群:Atopobiaceae (保护性),Enterococcus faecalis (保护性),Lactobacillus (B组) (保护性),Bacteroides eggerthii (致病性) 和Chloroflexales (致病性).
- 证明S-甲基半氨酸显著调解了Chloroflexales对sCJD风险的影响的8.8%.
- 已确立的Atopobiaceae (OR=0.527),E. faecalis (OR=0.647) 和Lactobacillus (OR=0.768) 的保护作用,以及B. eggerthii (OR=1.228) 和Chloroflexales (OR=3.455) 的致病作用.
结论:
- 该研究确立了肠道微生物群,CSF代谢物和sCJD之间的机械联系,突出了特定的微生物作为风险修饰因素.
- 研究结果表明,有可能使用已识别的微生物种群作为生物标志物用于早期sCJD风险评估,并作为预防益生菌候选人.
- 调节S-甲基半氨酸通路为sCJD提供了潜在的治疗策略,为扰乱子疾病中肠对脑传播提供了洞察力.
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