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

  • 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=18 340)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=0.968 2,95% CI:0.941 4~0.995 8,P=0.024 2)、瘤胃球菌属(genus. Ruminococcus1)(OR=0.959 4,95% CI:0.928 4~0.991 6,P=0.014 1)和梭菌目(order. Clostridiales)(OR=0.968 3,95% CI:0.941 3~0.995 8,P=0.024 3)菌群丰度升高可能会降低耳鸣发病风险;柔壁菌门(phylum. Tenericutes)(OR=1.022 1,95% CI:1.001 2~1.043 4,P=0.037 9)、柔膜菌纲(class. Mollicutes)(OR=1.022 1,95% CI:1.001 2~1.043 4,P=0.037 9)、脱硫弧菌属(genus. Desulfovibrio)(OR=1.031 4,95% CI:1.003 9~1.059 6,P=0.024 7)和未命名属(genus. unknowngenus)(OR=1.034 5,95% CI:1.014 4~1.055 0,P=0.000 7)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。

     

    Abstract:
    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 genomewide association study (GWAS) (n=18, 340) using the MiBioGen consortium, and the summary statistical data oftinnitus 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 relationship between gut microbiota and tinnitus. Cochran' s Q-test and MR Egger regression were used to verify thestability and heterogeneity of the results.
    Results  IVW analysis showed that an increase in the abundance ofclass.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.

     

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