Integrative multi-omics identifies coordinated alterations in the gut microbiome and in plasma and aqueous humor metabolomes in high myopic cataract

Growing evidence suggests that chronic inflammation contributes to the development of myopia, but the biological link between systemic processes and ocular changes remains poorly understood. In this study, we explored the gut-retina axis using a multi-omics approach in patients with high myopic cataract (HMC) compared with age-related cataract (ARC) controls. Fecal 16S rDNA sequencing revealed distinct microbial signatures in HMC, notably the enrichment of Lactobacillales and depletion of Roseburia, taxa associated with systemic inflammatory status. Metabolomic profiling of plasma and aqueous humor (AH) identified widespread alterations, with enrichment analyses highlighting pathways related to steroid hormone biosynthesis, PPAR signaling, and amino acid metabolism. Several metabolites correlated with axial length, and 4-phenolsulfonic acid in plasma and 5'-N-ethylcarboxamidoadenosine in AH showed the strongest discriminatory potential between HMC and ARC groups. While these findings are associative and require validation in larger, longitudinal cohorts, they suggest that systemic and ocular metabolic disturbances are closely linked to established high myopia. This study provides novel insights into the potential role of the gut-retina axis in myopia pathogenesis.