遗传决定性肠道微生物群对肺癌的因果关系:孟德尔的随机化研究
Huiwen Yu1,2, Chongde Pan1,2, Yu Jiang1
1Department of Thoracic Oncology and Surgery, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Journal of thoracic disease
|July 21, 2025
概括
这项研究使用了门德尔的随机化来研究肠道微生物群和肺癌 (LC) 之间的因果关系. 发现某些肠道细菌与LC风险有关,这表明潜在的治疗点.
科学领域:
- 微生物组研究的研究.
- 遗传学 遗传学 是一个
- 在瘤学瘤学.
背景情况:
- 肺癌 (LC) 是一个重大的全球健康挑战,生存率很低.
- 肠道微生物群和LC之间的关系是复杂的和争论的,观察性研究受到混因素的限制.
- 门德尔随机化 (MR) 用于探索肠道微生物群和LC之间的潜在因果关系.
研究的目的:
- 调查肠道微生物群组成和肺癌之间的潜在因果关系.
- 用遗传变异作为工具变量来进行强大的因果推断.
- 为了确定与LC风险相关的特定细菌种群.
主要方法:
- 使用了5,717,754个与肠道微生物群相关的单核酸多态 (SNP) 来自MiBioGen联盟作为仪器变量.
- 分析了211种细菌种类,使用16S rRNA测序数据,对共变量进行调整.
- 从IEU数据库 (11,348例,15,861例对照) 获取肺癌遗传统计数据,并应用逆方差加权 (IVW) 和同位分析.
主要成果:
- 在IVW分析中,特定肠道细菌与LC风险之间发现了显著的关联,包括Bifidobacteriales序列,Bifidobacteriaceae和Peptococcaceae家族,以及Clostridium sensu stricto*1,Collinsella*,Coprococcus*3,Erysipelatoclostridium*,Holdemanella*,Peptococcus*和Ruminiclostridium*6.
- 反向MR分析没有证据表明LC有因果影响肠道微生物群.
- 局部化分析表明肠道微生物群和LC之间有共同的遗传途径,涉及免疫调节和细胞增殖中的基因.
结论:
- 特定的肠道微生物组合因果关系与肺癌风险有关.
- 针对肠道微生物群的途径,如短链脂肪酸的生产,可能提供新的LC预防和治疗策略.
- 需要进一步的研究来探索肠道微生物群调节对改善LC结果的临床影响.
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