Abstract
Myopia, a major cause of irreversible visual impairment globally, is projected to affect about 25% of the world's population by 2025. Myopia progresses through childhood and adolescence, necessitating frequent prescription updates. While genetic and environmental factors are well-established contributors to myopia, emerging evidence suggests a significant role of the gut microbiota (GM) in its development, mainly through metabolic interactions. This study utilized a Mendelian Randomization (MR) approach to investigate the causal relationships between GM, metabolites, and myopia and pathological myopia (PM) progression. Using genetic variants as instrumental variables, we analyzed data from extensive genome-wide association studies (GWAS) to assess the impacts of 473 GM taxa and 233 metabolites on myopia risks. Our MR analysis identified specific GM taxa and metabolites with significant causal relationship to myopia and PM. Notably, lipid metabolites were found to mediate the effects of GM on myopia, suggesting a biochemical pathway that could influence ocular development and myopia progression. We also observed significant mediation effects, indicating that specific metabolites might serve as therapeutic targets to modulate myopia progression. The findings highlight the potential of GM and metabolites as novel targets for preventing or managing myopia. This study underscores the importance of further research into the gut-metabolite-eye axis to develop targeted interventions for myopia based on modifying the GM through diet, probiotics, or other means. Future studies should aim to elucidate the specific metabolites involved and their roles in ocular health, potentially offering new avenues for treatment.