Abstract
BACKGROUND: Several recent studies speculated that the gut microbiota is associated with sensorineural hearing loss (SNHL) and proposed the concept of the gut-inner ear axis. However, the causal effect of gut microbiota on SNHL is still unknown. In this study, we performed a two-sample Mendelian randomization (MR) analysis to estimate the causal effect of gut microbiota on SNHL. METHODS: Gut microbiota data were obtained from the largest available genome-wide association study (n = 18,340) conducted by the MiBioGen consortium. The summary statistics of SNHL were obtained from the FinnGen consortium R8 release data (28,310 cases and 302,750 controls). The causal effects were estimated with inverse-variance weighted, MR-Egger, and weighted median. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be associated with SNHL in forward Mendelian randomization analysis. We then performed sensitivity analyses, including Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, cML-MA-BIC, and leave-one-out analysis, to detect heterogeneity and pleiotropy. RESULTS: The inverse-variance weighted results suggested that Lachnospiraceae (UCG001) had a significant protective effect against SNHL (odds ratio = 0.85, 95% confidence interval: 0.78-0.93, P = 6.99 × 10(-4)). In addition, Intestinimonas (odds ratio = 0.89, 95% confidence interval: 0.82-0.97, P = 8.53 × 10(-3)) presented a suggestively protective effect on SNHL. Rikenellaceae (RC9gutgroup) (odds ratio = 1.08, 95% confidence interval: 1.02-1.15, P = 0.01) and Eubacterium (hallii group) (odds ratio = 1.12, 95% confidence interval: 1.00-1.24, P = 0.048) suggestively increase the risk of SNHL. The results of the reverse MR analysis showed that there is no significant causal effect of SNHL on the gut microbiota. No significant heterogeneity of instrumental variables or pleiotropy was detected. CONCLUSION: The evidence that the four genera mentioned above are associated with SNHL supports the hypothesis of a gut-inner ear axis. Our study provides microbial markers for the prevention and treatment of SNHL, and further studies are needed to explore the mechanisms of the gut microbiome-inner ear axis in health and diseases.