​​AMD Patients Have Imbalanced Gut Bacteria

Our gut—the intestinal commensal microbiota, specifically—is one possible systemic contributor to the pathogenesis of intestinal immune-mediated diseases. Inflammatory processes such as cytokine pathway and complement aberrations are known components of age-related macular degeneration (AMD) pathogenesis and progression; these may also be responsive to changes in gut microbiome. In a recent study, researchers investigated the link between advanced AMD changes in the microbiome, also considering factors like genetic risk and AREDS supplementation experience. They found that AMD is associated with “intestinal dysbiosis,” meaning an imbalance in gut bacteria, characterized by decreased bacterial diversity. The findings were reported in Ophthalmology Science. A higher genetic risk score for AMD was linked to lower gut microbial diversity, while AREDS supplementation was associated with increased bacterial diversity. Intestinal microbiota has a potential role in AMD pathogenesis and could be a target for future therapeutic interventions. Photo: Wikimedia commons/Ethan Hillman et al. Click image to enlarge. The study included 85 advanced AMD patients and 49 healthy controls; all subjects had their intestinal microbiota assessed through fecal rRNA sequencing and tests to quantify population levels.Advanced AMD was found to be associated with intestinal dysbiosis characterized by a decrease in gut bacterial diversity that inversely correlated with AMD genetic risk score, the authors wrote in their Ophthalmology Science paper. AMD patients showed distinct microbiota characteristics compared to healthy controls, with increased Proteobacteria and specific species like Prevotella and Desulfovibrio being enriched in AMD patients. Conversely, organisms like Oscillospira were more abundant in controls.Protoeobacteria has been reported to be enriched in patients with inflammatory bowel disease (IBD), multiple sclerosis (MS) and colorectal cancer. “On the other hand, Firmicutes, specifically, Clostridia, are depleted in MS patients, as in our AMD cohort. Both Gammaproteobacteria and Prevotella have been linked to non-alcoholic fatty liver disease and also linked to the AMD cohort, the authors explained in their paper. Numerous other intestinal organisms were studied for potential correlations with the presence or absence of disease in this population.“Overall, decreased gut bacterial alpha diversity has been associated with a number of diseases including cancer, IBD and cardiovascular disease, while in our study, it is associated with increased genetic risk in AMD, even after controlling for age,” the authors wrote in their study.Regarding gut immunity, there was a trend toward increased levels of specific bacteria, such as Prevotella, in subjects with higher AMD genetic risk. Of course, further investigation is needed before any modifications of care should be considered. “Although this finding may reflect altered host immune responses in AMD, no functional link has been established, and these associations should be considered hypothesis-generating,” the authors noted.They added that future studies incorporating functional immunological assays and longitudinal designs will be necessary to evaluate whether certain microbial species play a mechanistic role in AMD pathogenesis. It is possible that AMD could be driven by inflammasome-mediated chronic intestinal inflammation, the authors speculated.“Understanding how the gut microbiome and its metabolites interact with gut immunity and host genetics will allow us to further develop the microbiome to find potentially novel therapeutic targets in AMD,” the authors concluded in their paper. Click here for the journal source. Dadgar N, Fung K, McClintic S, et al. AREDS and genetic risk score are crucial determinants of intestinal microbial alterations in advanced age-related macular degeneration. Ophthalmol Sci. August 28, 2025. [Epub ahead of print.]This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.