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OA

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.