基于孟德尔随机化探讨肠道菌群与失眠的因果关联研究  

Based on Mendelian Randomization to Explore the Causal Relationship with Insomnia and Gut Microbiota

作　　者：郭玉梦 崔杨霖 张宪忠[2] GUO Yumeng;CUI Yanglin;ZHANG Xianzhong(Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Classic Department of Chinese Medicine,Rizhao Hospital of Traditional Chinese Medicine,Rizhao 276800,China)

机构地区：[1]山东中医药大学,山东省济南市250355 [2]山东省日照市中医医院中医经典科,276800

出　　处：《中国全科医学》2025年第8期954-961,共8页Chinese General Practice

基　　金：第七批全国老中医药专家学术经验继承工作项目(国中医人教函[2022]76号);日照市重点研发计划项目(公益性科技攻关)(2021ZDYF020213)。

摘　　要：背景随着失眠的发病率逐渐升高,其严重影响患者的精神及工作状态。肠道菌群被认为是失眠的一个危险因素,但目前存在相关证据较为缺乏的问题,难以准确认识二者之间的关系。目的使用两样本孟德尔随机化作为研究方法,探索肠道菌群与失眠之间的因果关系。方法使用MiBioGen联盟进行的最大可用全基因组关联研究荟萃分析(n=18340)中肠道菌群的汇总统计数据,根据预设的阈值提取与196种肠道微生物相对丰度显著相关的单核苷酸多态性(SNPs)作为工具变量(IVs)。失眠的汇总统计数据来自英国生物样本库(UK Biobank)(n=462341)。采用逆方差加权法(IVW)、MR-Egger回归、加权中位数法(WME)、加权众数法(WM)等检测肠道菌群与失眠之间的因果关系,其中以IVW法为主,根据效应指标优势比(OR)和95%置信区间(CI)评估结果。结合敏感性分析、异质性检验、基因多效性检验和异常值检验(MR-PRESSO)等方法来验证结果的稳定性和可靠性。并对发现与失眠有因果关系的菌群进行反向孟德尔随机化分析。结果IVW结果显示蔷薇菌属(OR=0.787,95%CI=0.671~0.923,PFDR=0.016)、丹毒杆菌属(OR=0.880,95%CI=0.794~0.976,PFDR=0.077)、副普雷沃菌属(OR=0.891,95%CI=0.801~0.991,PFDR=0.083)、瘤胃球菌属UCG014组(OR=0.818,95%CI=0.697~0.961,PFDR=0.072)、巴斯德菌科(OR=0.897,95%CI=0.814~0.988,PFDR=0.081)、巴斯德菌目(OR=0.897,95%CI=0.814~0.988,PFDR=0.094)和失眠有关,未发现IVs存在基因多效性或显著异质性。根据反向孟德尔随机化分析结果,失眠对肠道菌群无显著的因果影响。结论蔷薇菌属、丹毒杆菌属、副普雷沃菌属、瘤胃球菌属UCG014组、巴斯德菌科、巴斯德菌目6种肠道菌群丰度与失眠的发病风险呈负相关,即丰度降低会增加失眠的发病风险,为失眠的保护因素。Background As the prevalence of insomnia is gradually increasing,it is seriously affecting the mental and work status of patients.The gut microbiota is considered to be a risk factor for insomnia,but there is a relative lack of evidence to accurately recognize the relationship between gut microbiota and insomnia.Objective Using two-sample Mendelian randomization as a research methodology to explore the causal relationship between gut microbiota and insomnia.Methods Single nucleotide polymorphisms(SNPs)significantly associated with the relative abundance of 196 gut microorganisms were extracted as instrumental variables(IVs)according to predefined thresholds using pooled statistics of the gut microbiota from the largest available genome-wide meta-analysis of association studies conducted by the MiBioGen consortium(n=18340).Pooled statistics for insomnia were obtained from the UK Biobank(n=462341).Inverse variance weighting(IVW),MR-Egger regression,weighted median(WME),and weighted multinomial(WM)were used to detect the causal relationship between gut microbiota and insomnia,with IVW being the predominant method,and the results were assessed according to the effect indicator dominance ratio(OR)and 95%confidence interval(CI).Sensitivity analysis,heterogeneity test,gene multiplicity test,MR multiplicity residual and outlier test(MR-PRESSO)were combined to verify the stability and reliability of the results.Reverse Mendelian randomization analysis was also performed on the colonies found to be causally associated with insomnia.Results IVW results showed that genus_Roseburia(OR=0.787,95%CI=0.671-0.923,PFDR=0.016),genus_Erysipelatoclostridium(OR=0.880,95%CI=0.794-0.976,PFDR=0.077),genus_Paraprevotella(OR=0.891,95%CI=0.801-0.991,PFDR=0.083),genus_Ruminococcaceae UCG014(OR=0.818,95%CI=0.697-0.961,PFDR=0.072),family_Pasteurellaceae(OR=0.897,95%CI=0.814-0.988,PFDR=0.081),order_Pasteurellales(OR=0.897,95%CI=0.814-0.988,PFDR=0.094)were associated with insomnia,and no genetic pleiotropy or significant heterogeneity of IVs was

关 键 词：肠道菌群 失眠 孟德尔随机化 因果关联 

分 类 号：R741[医药卫生—神经病学与精神病学]