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运用孟德尔随机化探索肠道微生物与非酒精性脂肪性肝病的因果关联OACSTPCD

Using Mendelian randomization to explore the causal association between gut microbiota and nonalcoholic fatty liver disease

中文摘要英文摘要

目的 采用孟德尔随机化分析方法探讨肠道微生物与非酒精性脂肪性肝病(NAFLD)之间的因果关联.方法 肠道微生物群的遗传工具变量是从18 340例参与者的全基因关联研究确定的,NAFLD的汇总统计数据来自FinnGen数据库,该数据库提供了 894例NAFLD病例的数据和217898例对照,使用IVW方法作为主要分析,为了检验结果的稳健性,还采用了 MR-Egger法、WM法、Simple Mode法、Weighted Mode法进行了孟德尔随机化分析,并进行异质性检验、敏感性分析、多效性分析.结果 丙型变形菌纲IVW结果显示(OR=0.621,95%CI=0.412~0.934,P=0.022);肠杆菌科 IVW 结果显示(OR=1.481,95%CI=1.069~2.053,P=0.018);毛螺菌科 IVW 结果显示(OR=1.405,95%CI=1.036~1.904,P=0.029);普氏菌属 7 IVW结果显示(OR=0.834,95%CI=0.714~0.974,P=0.021);普氏菌属 9 IVW 结果显示(OR=1.251,95%CI=1.025~1.527,P=0.027);脱硫弧菌目IVW结果显示(OR=0.714,95%CI=0.519~0.982,P=0.038);肠杆菌目IVW 结果显示(OR=1.481,95%CI=1.069~2.053,P=0.018).并且异质性检验不存在异质性,敏感性分析均显示稳健,且未显示多效性.结论 丙型变形菌纲、普氏菌属7、脱硫弧菌目、肠杆菌科、毛螺菌科、普氏菌属9、肠杆菌目种类的肠道微生物与NAFLD之间可能存在因果关系.

Objective To explore the causal association between gut microbes and non-alcoholic fatty liver disease(NAFLD)by Mendelian randomisation analysis.Methods Genetic instrumental variables for gut microbiota were identified from a gene-wide association study of 18 340 participants,and summary statistics for NAFLD were ob-tained from the FinnGen database,which provided data on 894 NAFLD cases and 217 898 controls using the IVW method as the primary analysis.In order to test the robustness of the results,MR-Egger method,WM method,Simple Mode method,Weighted Mode method were used for Mendelian randomisation analysis,and heterogeneity test,sensitivity analysis,and multiplicity analysis were performed.Results class Gammaproteobacteria IVW re-sults showed(OR=0.621,95%CI=0.412~0.934,P=0.022);family Enterobacteriaceae IVW results showed(OR=1.481,95%CI=1.069~2.053,P=0.018);genus Lachnospiraceae IVW results showed(OR=1.405,95%CI=1.036~1.904,P=0.029);genus Prevotella7 IVW results showed(OR=0.834,95%CI=0.714~0.974,P=0.021);genus Prevotella9 IVW results showed(OR=1.251,95%CI=1.025~1.527,P=0.027);order Desulfovibrionales IVW results showed(OR=0.714,95%CI=0.519~0.982,P=0.038);or-der Enterobacteriales IVW results showed(OR=1.481,95%CI=1.069~2.053,P=0.018).And there was no heterogeneity in the heterogeneity test,and the sensitivity analyses all showed robustness and no pleiotropy was found.Conclusion This study implicates class Gammaproteobacteria,family Enterobacteriaceae,genus Lachno-spiraceae,genus Prevotella7,genus Prevotella9,order Desulfovibrionales,order Enterobacteriales seven species of gut microorganisms have a causal relationship with NAFLD.

吴闵;安祯祥;何远利;何松;刘闯;孙凯

贵州中医药大学第一临床医学院,贵阳 550001贵州中医药大学第一临床医学院,贵阳 550001||贵州中医药大学第一附属医院消化内科,贵阳 550001贵州中医药大学第一临床医学院,贵阳 550001||贵州中医药大学第一附属医院老年病科,贵阳 550001

临床医学

肠道微生物非酒精性脂肪性肝病孟德尔随机化

gut microbiotanon-alcoholic fatty liver diseaseMendelian randomization

《安徽医科大学学报》 2024 (002)

基于内质网—线粒体选择性自噬交互作用探讨肝星状细胞活化机制及扶脾柔肝方的干预效应

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国家自然科学基金(编号:82160893);国家中医药管理局第五批全国中医临床优秀人才研修项目(编号:国中医药人教函[2022]1号);贵州中医药大学中医脾胃病科技创新人才团队建设(编号:贵中医TD[2022]005号)

10.19405/j.cnki.issn1000-1492.2024.02.009

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