Abstract
BACKGROUND: High myopia has become a major cause of blindness worldwide and can contribute to emotional deficits through its impact on the central nervous system. The potential crosstalk with gut microbiome positions high myopia as a valuable model for studying the eye-brain-gut axis, highlighting the intricate interplay between visual health, neurological function, and the gut microbiome. Understanding these connections is crucial from a predictive, preventive, and personalized medicine (PPPM) perspective, as it may reveal novel intervention targets for managing both visual and mental health. WORKING HYPOTHESIS AND METHODOLOGY: In our study, we hypothesized that visual stimuli associated with high myopia may lead to gut microecological dysregulation, potentially triggering mood disorders such as anxiety and depression. To test this hypothesis, we assessed genetic associations between high myopia (N = 50,372) and depression (N = 674,452) as well as anxiety (N = 21,761) using inverse variance weighted as the primary analytical method. We also investigated the potential mediating role of the gut microbiome (N = 18,340). The findings were validated in an independent cohort and summarized through meta-analysis. RESULTS: A genetic causal relationship between high myopia and anxiety was found (odds ratio [OR] = 8.76; 95% confidence interval [CI], 2.69-28.54; p = 3.16 × 10(-4)), with 20.3% of the effect mediated by the gut microbiome family Lactobacillaceae (β = 0.517; 95% CI, 0.104-1.090; p = 0.037). The analysis also showed a suggestive causal relationship between high myopia and depression (OR = 1.25; 95% CI, 1.00-1.57; p = 0.048). CONCLUSIONS: Our study shows that high myopia causes anxiety via the Lactobacillaceae family of the gut microbiome, supporting the eye-brain-gut axis concept. This underscores the need to shift from reactive to predictive, preventive, and personalized medicine (PPPM). Targeting Lactobacillaceae offers novel insights for early intervention and personalized treatment of high myopia-related anxiety and sheds light on interventions for other vision-related brain disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00387-z.