Background: Sensorineural hearing loss (SNHL) is a multifactorial disorder with potential links to various physiological systems, including the cardiovascular system via blood lipid levels such as triglycerides (TG). This study investigates the causal relationship between TG levels and SNHL using Mendelian randomization (MR), which offers a method to reduce confounding and reverse causality by using genetic variants as instrumental variables. Methods: Utilizing publicly available genome-wide association study (GWAS) data, we performed a two-sample MR analysis. The initial analysis unveiled a causal relationship between TG (GWAS ID: ebi-a-GCST90018975) and SNHL (GWAS ID: finn b-H8_HL_SEN-NAS). Subsequent analysis validated this through MR with a larger sample size for TG (GWAS ID: ieu-b-111) and SNHL. To conduct the MR analysis, we utilized several methods including inverse-variance weighted (IVW), MR Egger, weighted median, and weighted mode. We also employed Cochrane’s Q test to identify any heterogeneity in the MR results. To detect horizontal pleiotropy, we conducted the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test. We performed a leave-one-out analysis to assess the sensitivity of this association. Finally, a meta-analysis of the MR results was undertaken. Results: Our study found a significant positive correlation between TG and SNHL, with OR values of 1.14 (95% CI: 1.07–1.23, p < 0.001) in the IVW analysis and 1.09 (95% CI: 1.03–1.16, p < 0.006) in the replicate analysis. We also found no evidence of horizontal pleiotropy or heterogeneity between the genetic variants (p > 0.05), and a leave-one-out test confirmed the stability and robustness of this association. The meta-analysis combining the initial and replicate analyses showed a significant causal effect with OR values of 1.11 (95% CI: 1.06–1.16, p = 0.01). Conclusion: These findings indicate TG as a risk factor for SNHL, suggesting potential pathways for prevention and intervention in populations at risk. This conclusion underscores the importance of managing TG levels as a strategy to mitigate the risk of developing SNHL.

Uncontrolled neutrophilic inflammation and Nlrp3 inflammasome activation contribute to a wide range of mucosal disorders, yet the endogenous circuits that constrain this process at the cellular level remain poorly defined. Using single-cell RNA sequencing of the Eustachian tube in a rat model of ovalbumin-induced otitis media with effusion (OME), we identified massive neutrophil infiltration coupled with intrinsic Nlrp3 inflammasome activation as dominant features of the early OME microenvironment. Systematic intercellular communication analysis using CellChat predicted a disease-specific Annexin A1 (Anxa1)–formyl peptide receptor 2 (Fpr2) ligand-receptor axis converging on infiltrating neutrophils. Intratympanic pre-treatment with Anxa1 dose-dependently suppressed Nlrp3, IL-1β, and IL-18 without altering the priming cytokine TNF-α, reduced middle ear effusion volume on micro-CT, and preserved ciliary and goblet cell architecture. Co-administration of the Fpr2 antagonist WRW4 reversed the Anxa1-mediated reduction in IL-18 and middle ear effusion, indicating that the Anxa1-Fpr2 axis functions as an Fpr2-dependent checkpoint that limits inflammasome amplification rather than initial inflammatory priming. These findings identify a pharmacologically tractable, neutrophil-targeted brake on the Nlrp3 inflammasome and provide a mechanism-based direction for local anti-inflammatory therapy in OME.