基于孟德尔随机化的肠道菌群与耳鸣之间的因果关系  

The causal relationship between gut microbiota and tinnitus based on Mendelian randomization

作　　者：梁茵菲 周靖诗 张姝琪 李凌伟 顾晶[1] 温志阳 吴冬雪 黎志成[1] 曾祥丽[1] LIANG Yinfei;ZHOU Jingshi;ZHANG Shuqi;LI Lingwei;GU Jing;WEN Zhiyang;WU Dongxue;LI Zhicheng;ZENG Xiangli(Department of Otolaryngology-Head and Neck Surgery,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院耳鼻咽喉—头颈外科,广州510630

出　　处：《广西医科大学学报》2024年第10期1390-1397,共8页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.82171151);广州市科技计划产学研协同创新重大专项(No.201704030081)。

摘　　要：目的:基于孟德尔随机化(MR)研究方法探索肠道菌群与耳鸣之间的因果关系。方法:使用MiBioGen联盟开展的全基因组关联研究(GWAS)(n=18340)个体中肠道微生物群的数据,与耳鸣的汇总统计数据——来自英国生物样本数据库发布的数据进行两样本MR研究。使用统计模型逆方差加权(IVW)为主要结果,简单模式法(simple mode)、模型选择法(MR_Egger)、加权中位数法(weighted median)和加权模型(weighted mode)作为补充检验,分析肠道微生物群与耳鸣之间的因果关系,Cochran的Q检验和MR-Egger回归法验证结果的稳定性和异质性。结果:IVW分析显示,梭菌纲(class.Clostridia)(OR=0.9682,95%CI:0.9414~0.9958,P=0.0242)、瘤胃球菌属(genus.Ruminococcus1)(OR=0.9594,95%CI:0.9284~0.9916,P=0.0141)和梭菌目(order.Clostridiales)(OR=0.9683,95%CI:0.9413~0.9958,P=0.0243)菌群丰度升高可能会降低耳鸣发病风险;柔壁菌门(phylum.Tenericutes)(OR=1.0221,95%CI:1.0012~1.0434,P=0.0379)、柔膜菌纲(class.Mollicutes)(OR=1.0221,95%CI:1.0012~1.0434,P=0.0379)、脱硫弧菌属(genus.Desulfovibrio)(OR=1.0314,95%CI:1.0039~1.0596,P=0.0247)和未命名属(genus.unknowngenus)(OR=1.0345,95%CI:1.0144~1.0550,P=0.0007)菌群丰度升高可能会增加耳鸣发病的风险。工具变量未发现水平多效性及异质性。结论:梭菌纲、瘤胃球菌属和梭菌目可能是耳鸣的潜在保护菌群,柔壁菌门、柔膜菌纲、脱硫弧菌属和未命名属可能是耳鸣的潜在危害因素。Objective:To explore the causal relationship between gut microbiota and tinnitus based on Mendelian randomization(MR)research method.Methods:Data on the gut microbiota in individuals from the genome wide association study(GWAS)(n=18,340)using the MiBioGen consortium,and the summary statistical data of tinnitus were obtained from published data in the UK Biobank for a two sample MR study.Using statistical model inverse variance weighting(IVW)as the main result,simple mode method,model selection method(MR-Egger),weighted median method,and weighted model were used to supplement the examination of the causal rela-tionship between gut microbiota and tinnitus.Cochran's Q-test and MR Egger regression were used to verify the stability and heterogeneity of the results.Results:IVW analysis showed that an increase in the abundance of class.Clostridia(OR=0.9682,95%CI:0.9414-0.9958,P=0.0242),genus.Ruminococcus 1(OR=0.9594,95%CI:0.9284-0.9916,P=0.0141),and order.Clostridiales(OR=0.9683,95%CI:0.9413-0.9958,P=0.0243)might reduce the risk of tinnitus;the increased abundance of phylum.Tenericutes(OR=1.0221,95%CI:1.0012-1.0434,P=0.0379),class.Mollicutes(OR=1.0221,95%CI:1.0012-1.0434,P=0.0379),genus.Desulfovibrio(OR=1.0314,95%CI:1.0039-1.0596,P=0.0247),and genus.unknowngenus(OR=1.0345,95%CI:1.0144-1.0550,P=0.0007)might increase the risk of tinnitus.No horizontal pleiotropy or heterogeneity was found in instrumental variables.Conclusion:Class.Clostridia,genus.Ruminococcus 1,and order.Clostridiales may be potential protective bacterial groups for tinnitus,while phylum.Tenericutes,class Mollicutes,genus.Desulfovibrio,and genus.unknowngenus may be potential risk factors for tinnitus.

关 键 词：耳鸣 肠道菌群 孟德尔随机化 因果推断 

分 类 号：R740[医药卫生—神经病学与精神病学] R764.45[医药卫生—临床医学]