中华耳科学杂志2026，Vol.24Issue(5)：429-435,7.DOI:10.3969/j.issn.1672-2922.2026.05.009
肠道菌群与免疫炎症对突发性耳聋的中介孟德尔随机化研究
Causal effects of gut microbiota,immune cells,and inflammatory factors in idiopathic sudden sensorineural hearing loss:a mendelian randomization mediation
张笑立 1冯剑波 2祖旭宇 2谭国林3
作者信息
- 1. 南华大学附属第一医院耳鼻喉头颈外科,衡阳 421001
- 2. 南华大学附属第一医院肿瘤研究所,衡阳 421001
- 3. 中南大学湘雅三医院耳鼻喉头颈外科,长沙 410013
- 折叠
摘要
Abstract
Objective To systematically investigate the mediating effects of immune cells and inflammatory factors in the pathogenesis of sudden sensorineural hearing loss(ISSNHL)associated with gut microbiota through a three-stage Mendelian randomization(MR)framework.Methods Genome-wide association studysummary statistics were obtained from international databases for gut microbiota(211 taxonomic units),immune cells(731 phenotypes),inflammatory factors(91 cytokines),and ISSNHL(3861 cases vs.437 331 controls).Instrumental variables were selected using genome-wide significance thresholds(P<5×10-6).A two-sample MR framework was implemented,including:Inverse-variance weighted combined with MR-Egger regression and weighted median methods;Horizontal pleiotropy(MR-Egger intercept)and heterogeneity(Cochran's Q test);Delta method to quantify indirect effects via immune-inflammatory pathways.Results MR analyses identified eight gut microbial taxa(OR=0.475～1.642),two immune cells(CD19+IgD-CD24-B cells and CD33dimHLA-DR+CD11b-myeloid cells),and two inflammatory factors(stem cell factor and Axin-1)showing significant causal associations with ISSNHL(P<0.05).Mediation MR revealed that genus Phascolarctobacterium reduced ISSNHL risk by elevating circulating Axin-1 levels,accounting for 7.5%of the total effect(P=0.025).All associations were robust against pleiotropy(MR-Egger intercept,P>0.05)and heterogeneity(Q-statistic,P>0.05).Conclusions This study provides the first evidence that gut microbiota may influence ISSNHL pathogenesis through Axin-1-mediated immunoregulation,highlighting novel therapeutic targets for cochlear microenvironment modulation.关键词
突发性耳聋/肠道菌群/孟德尔随机化/免疫细胞/炎症因子Key words
idiopathic sudden sensorineural hearing loss/gut microbiota/mendelian randomization/immune cells/inflammatory cytokines引用本文复制引用
张笑立,冯剑波,祖旭宇,谭国林..肠道菌群与免疫炎症对突发性耳聋的中介孟德尔随机化研究[J].中华耳科学杂志,2026,24(5):429-435,7.
