A new case–control study published in Ophthalmology Science has provided compelling evidence that the gut microbiome is significantly altered in patients with advanced age-related macular degeneration (AMD), with both genetic risk and AREDS supplementation emerging as crucial determinants of microbial diversity and composition.
The study enrolled 85 patients with advanced AMD (geographic atrophy or neovascular AMD) and 49 age-similar controls. Using 16S rRNA sequencing, the investigators characterized gut microbial composition, diversity, immunoglobulin A (IgA) binding, and inferred metabolic pathways. Importantly, the team also integrated genetic risk scores (GRS) and data on AREDS supplement use, allowing them to disentangle host and environmental influences on the intestinal microbiome.
A central finding was that higher AMD genetic risk scores correlated with reduced gut microbial alpha diversity. Conversely, AREDS supplementation was associated with increased microbial diversity, even after adjusting for confounders such as age and gender. These results suggest a dynamic interplay: genetics appear to predispose AMD patients to gut dysbiosis, while AREDS formulations may partially mitigate this effect.
“Intestinal dysbiosis” – meaning decreased gut bacterial diversity – was found to be associated with advanced AMD (i.e. combined nAMD and GA). The microbial profiles of AMD patients were distinct from controls. Proteobacteria, particularly Gammaproteobacteria, were enriched in AMD, while Firmicutes (Clostridia) were depleted. At the genus level, Prevotella, Desulfovibrio, Oscillospira, and Ruminococcaceae subgroups were differentially abundant. Notably, Prevotella emerged consistently across subgroup analyses, including in patients not taking AREDS supplements, reinforcing its potential role in AMD pathobiology.
This is the largest study to date examining the gut–retina axis in AMD, and the first to demonstrate clear associations between genetic risk, AREDS supplementation, microbial diversity, and gut immunity. For clinicians, several implications arise:
Screening and prevention: Gut microbiome composition may serve as a potential biomarker for AMD risk stratification in the future.
Therapeutic potential: Modulating the microbiome through diet, probiotics, or targeted interventions could complement current anti-VEGF and AREDS-based strategies.
Patient management: The findings reinforce the role of AREDS supplementation not only in retinal physiology, but also in maintaining microbial diversity, especially in genetically predisposed patients.
The study underscores the triangular relationship between genetics, nutrition, and the gut microbiome in shaping AMD pathogenesis. By revealing that AREDS supplementation may counterbalance genetically driven microbial loss of diversity, the findings highlight new avenues for personalized AMD care, and point toward the microbiome as a potential therapeutic target for AMD pathogenesis.
