海南医学院学报2024，Vol.30Issue(22)：1727-1734,8.DOI:10.13210/j.cnki.jhmu.20240531.001
肠道菌群及其代谢通路与胰腺癌的因果关系-两样本孟德尔随机化分析
Two-sample Mendelian randomization:Gut microbiota and its metabolic pathways and pancreatic cancer
摘要
Abstract
Objective:To investigate the causal relationship between gut microbiota and its metabolic pathways and pancreatic cancer by performing two-sample Mendelian randomization analysis.Methods:GWAS data of gut microbiota and its metabolic pathways was obtained from The Dutch Microbiome Project and pancreatic cancer GWAS comes from The FinnGen Biobank.In-dependent genetic loci significantly correlated with the relative abundance of gut microbiota and the enrichment of bacterial path-ways were extracted as instrumental variables according to P<1×10-5,and F>10.We performed the inverse variance weighting method for the main analysis,and the effect size was determined by the OR and 95%CI.In the sensitivity analysis,multiple meth-ods such as the leave-one-out method,Cochran's Q test,MR-Egger method,and MR-PRESSO were employed to ensure the sta-bility and reliability of the analysis results.Results:The OR and 95%CI of Prevotella copri and Streptococcus thermophilus were 1.34(1.06-1.68)and 1.28(1.01-1.63),respectively.The OR and 95%CI of the three metabolic pathways of urea cycle,unsatu-rated fatty acid synthesis and N10-formyltetrahydrofolate synthesis were 0.71(0.51-0.99),0.73(0.57-0.93)and 0.72(0.54-0.96),respectively.The OR and 95%CI of L-methionine synthesis,allantoin degradation to glyoxyl Ⅲ and ubiquinol 8 synthesis were 1.40(1.02-1.91),1.18(1.00-1.38)and 1.42(1.15-1.76),respectively.The leave-one-out analysis showed stable results,with no instrumental variables that had a strong influence on the results.In addition,the sensitivity analysis also excluded the influence of heterogeneity and horizontal gene pleiotropy on the estimation of causal effect.Conclusion:Prevotella copri and Streptococcus thermophilus have potential causal relationship with pancreatic cancer.Enrichment of three metabolic pathways of urea cycle,Escoli unsaturated fatty acid synthesis and N10-formyltetrahydrofolate synthesis can reduce the risk of pancreatic can-cer,while enrichment of three metabolic pathways of L-methionine synthesis,allantoin degradation to glyoxyl Ⅲ and panquinol-8 synthesis can increase the risk of pancreatic cancer.关键词
胰腺癌/肠道菌群/代谢通路/孟德尔随机化Key words
Pancreatic cancer/Gut microbiota/Metabolic pathway/Mendelian randomization分类
医药卫生引用本文复制引用
殷智洪,彭晓杰,林源华,黄海溶..肠道菌群及其代谢通路与胰腺癌的因果关系-两样本孟德尔随机化分析[J].海南医学院学报,2024,30(22):1727-1734,8.基金项目
This study was supported by the High-Level Talent Project of Hainan Provincial Natural Science Foundation(821RC745) 海南省自然科学基金高层次人才项目(821RC745) （821RC745）
