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

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

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18340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 18340 participants,and summary statistics for NAFLD were obtained from the FinnGen database,which provided data on 894 NAFLD cases and 217898 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 results 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);order 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 Lachnospiraceae,genus Prevotella7,genus Prevotella9,order Desulfovibrionales,order Enterobacteriales seven species of gut microorganisms have a causal relationship with NAFLD.