Metagenomic Profiling of the Gut Microbiome in Age-Related Macular Degeneration-A Pilot Study.

<b>Background/Objectives:</b> Age-related macular degeneration (AMD) is a multifactorial retinal disease involving inflammatory, metabolic, and genetic factors. Increasing evidence suggests that the gut microbiome may contribute to systemic pathways involved in retinal homeostasis. This exploratory pilot study investigated gut microbiome alterations in AMD patients and controls using long-read whole-genome sequencing. <b>Methods:</b> Bacterial DNA was extracted from fecal samples and analyzed using Oxford Nanopore sequencing, followed by taxonomic profiling, alpha and beta diversity analyses, and differential abundance testing. <b>Results:</b> AMD patients showed significantly reduced microbial diversity, reflected by lower richness, Shannon and Simpson indices. Species-level beta diversity analyses revealed significant differences in microbial community composition, particularly with Bray-Curtis metrics, alongside increased inter-individual microbial heterogeneity in AMD samples. Differential abundance analyses identified the depletion of several potentially beneficial commensal taxa, including <i>Faecalibacterium prausnitzii</i> and <i>Parabacteriodes distasonis</i>, whereas <i>Staphylococcus aureus</i> was enriched in AMD patients. Comparisons between wet and dry subtypes showed no significant differences in alpha or beta diversity. <b>Conclusions:</b> Overall, the findings support the presence of gut microbial dysbiosis in AMD characterized by reduced diversity, abundance-driven community shifts, and increased microbiome heterogeneity. Given the small cohort size, cross-sectional design and lack of functional analysis, these results should be considered preliminary and hypothesis-generating.