Gut microbiota dysbiosis and altered fecal metabolome in patients with age-related cataract

Age-related cataract (ARC) is a leading cause of vision loss with incompletely understood mechanisms. Emerging evidence suggests the gut microbiota can influence ocular health, yet the gut-eye connection in cataract remains unexplored. We characterized gut microbial communities and fecal metabolic profiles in 30 ARC patients and 30 healthy controls using 16S rDNA gene sequencing, untargeted LC-MS metabolomics, and targeted GC-MS for short-chain fatty acids (SCFAs). While alpha- and beta-diversity were comparable between groups, ARC patients exhibited significant dysbiosis, including reduced Gut Microbiome Health Index, increased Microbial Dysbiosis Index, higher relative abundance of Bifidobacterium and Klebsiella, and depletion of butyrate-producing taxa (Faecalibacterium, Clostridia). Fecal metabolomic profiles distinctly separated ARC patients from controls, with pathway analysis highlighting disruptions in glycerophospholipid and choline metabolism. Targeted analysis confirmed significant depletion of acetate, propionate, and butyrate in ARC patients (all P< 0.01), which positively correlated with beneficial genera abundance. This integrative study reveals that ARC patients harbor gut microbial dysbiosis and distinct fecal metabolomic signatures, notably a loss of SCFA-producing bacteria and anti-inflammatory SCFAs. These findings support a novel gut-eye axis in cataract pathogenesis and suggest that gut-derived microbial and metabolic biomarkers may aid in non-invasive risk assessment, while microbiome-targeted interventions could offer new preventive or therapeutic avenues.