Fecal Microbial and Metabolomic Profiles in Patients with Age-Related Macular Degeneration

Abstract

Purpose : Dietary modifications have proven to be an effective measure in slowing progression of early stages of age-related macular degeneration (AMD), and studies have recently begun to explore the gut microbiome as a possible link between such environmental factors and disease pathogenesis. However, it remains unexplored how microbiota dysbiosis differs between stages of disease as well as if the abundance of protective gut-derived metabolites is also altered. We performed an exploratory pilot study to investigate the gut microbiome composition and metabolite abundance in AMD patients compared to age-matched controls.

Methods : Fasted stool samples were collected from 22 eligible patients presenting to the University of Chicago. Subjects were categorized into either control, intermediate AMD, or advanced AMD groups based on clinical presentation. 16S rRNA amplicon sequencing and standard chromatography-mass spectrometry methods were used to identify taxonomy for bacteria composition analysis and abundance of short chain fatty acids (SCFAs) and bile acids (BAs), respectively. Genetic testing was used to investigate the presence of 14 high-risk SNPs associated with AMD in disease patients.

Results : 43 differentially abundant genera were present between the control, intermediate, and advanced groups. Several taxa with known roles in immunologic pathways and implicated in various systemic conditions such as Desulfovibrionales (q=0.102), Peptococcaceae (q=0.021), and Terrisporobacter (q=1.16e-03) were greater in advanced AMD patients compared to intermediate. Advanced AMD subjects had decreased abundance of 9 key protective SCFAs including acetate (p=0.003), butyrate (p=0.032), and propionate (p=0.021), and 5 BAs such as taurocholic acid (p=0.020) and tauroursodeoxycholic acid (p=0.015). Such metabolites are important for the regulation of the mucosal immune system and their effects are actively being studied in the context of pathogenesis of several neurologic and retinal diseases. No significant differences in the frequency of SNPs were found between intermediate and advanced AMD cohorts.

Conclusions : 16S rRNA sequencing and metabolomic analysis revealed significant differences between the gut microbiome profiles across cohorts, strongly suggesting a link between gut health and AMD pathogenesis. Future studies are needed to define this relationship and explore its underlying mechanisms more precisely.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.