摘要
目的通过孟德尔随机化(MR)方法探究东亚人群肠道菌群(GM)与原发性肝癌(PLC)之间的潜在因果关系。方法本研究遵循STROBE-MR指南,采用基于相关性、独立性和排他性假设的MR分析。暴露数据来自3432名中国人的全基因组关联研究(GWAS)汇总数据,涵盖500种GM特征。PLC的数据来自日本数据库(n=161323)和IEU open GWAS平台(n=197611)。综合运用了逆方差加权法(IVW)、加权中位数法、MR-Egger法以及贝叶斯加权MR等多种方法,评估GM与PLC之间的因果关系。结果特定GM如Selenomonas、Porphyromonas endodontalis、Gemella sanguinis和Clostridium butyricum与PLC风险的增加相关;而Alistipes shahii及Bifidobacterium catenulatum-Bifidobacterium pseudocatenulatum复合群可能具有保护作用。多种MR分析方法的应用增强了研究结果的可靠性和稳健性。结论本研究从遗传学的角度揭示GM在PLC发生发展中作用,并突出了肠道微生物群在PLC发病机制中的关键作用。
Objective To investigate the potential causal relationship between gut microbiota(GM)and primary liver cancer(PLC)in East Asian population by Mendelian randomization(MR)analysis.Methods This study was conducted following the STROBE-MR guidelines.MR analysis was performed based on the assumptions of relevance,independence and exclusion restriction.The exposure data were collected from genome-wide association study(GWAS)summary statistics in 3432 Chinese,covering 500 GM features.The data of PLC were obtained from Japanese Database(n=161323)and IEU Open GWAS platform(n=197611).The inverse variance weighted(IVW),weighted median,MR-Egger and Bayesian weighted MR methods were used to evaluate the causal relationship between GM and PLC.Results Specific GM such as Selenomonas,Porphyromonas endodontalis,Gemella sanguinis and Clostridium butyricum were associated the increased risk of PLC.However,Alistipes shahii and Bifidobacterium catenulatum-Bifidobacterium pseudotenatum complex might exert protective effects.The application of multiple MR analysis methods enhanced the reliability and robustness of the research results.Conclusions This study provides novel understanding of the role of GM in the incidence and progression of PLC from the genetic perspective and highlights the key role of GM in the pathogenesis of PLC.
作者
薛伟伟
杜凯豪
汪占金
东小鸽
何洁洁
罗兰明慧
蒋威
王展
Xue Weiwei;Du Kaihao;Wang Zhanjin;Dong Xiaoge;He Jiejie;Rolan Minghui;Jiang Wei;Wang Zhan(Clinical Medical College of Qinghai University,Xining 810000,China;Department of Hepatobiliary and Pancreatic Surgery,Qinghai University Affiliated Hospital,Xining 810000,China;Transformation and Application of Engineering Medicine,Qinghai University Affiliated Hospital,Xining 810000,China)
出处
《中华肝脏外科手术学电子杂志》
2026年第1期79-88,共10页
Chinese Journal of Hepatic Surgery(Electronic Edition)
基金
国家自然科学基金(82160131)
中国科学院“西部之光”青年学者项目。
关键词
肠道菌群
原发性肝癌
孟德尔随机化
因果
东亚
Gut microbiome
Primary liver cancer
Mendelian randomization
Causality
East asia
