Fecal Microbial Profiles and Short-Chain Fatty Acid/Bile Acid Metabolomics in Patients With Age-Related Macular...

Age-related macular degeneration (AMD) is a multifactorial disease, and studies have implicated the role of gut microbiota in its pathogenesis. However, characterization of microbiome dysbiosis and associated microbial-derived metabolomic profiles across AMD stages remains unknown. In this pilot study, we explored how gut microbiome composition and gut-derived metabolites differ in AMD.

Our pilot study analyzed fasted stool samples that were collected from 22 patients at a tertiary academic center. Subjects were classified as control, intermediate AMD, or advanced AMD based on clinical presentation. 16S rRNA amplicon sequencing and standard chromatography-mass spectrometry methods were used to identify bacterial taxonomy composition and abundance of short-chain fatty acids (SCFAs) and bile acids (BAs), respectively. Genetic testing was used to investigate the frequency of 14 high-risk single nucleotide polymorphisms (SNPs) associated with AMD in the AMD cohort.

Forty-three differentially abundant genera were present among the control, intermediate, and advanced groups. Taxa with known roles in immunologic pathways, such as Desulfovibrionales (q = 0.10) and Terrisporobacter (q = 1.16e-03), were in greater abundance in advanced AMD patients compared to intermediate. Advanced AMD patients had decreased abundance of 12 SCFAs, including acetate (P = 0.002), butyrate (P = 0.04), and propionate (P = 0.01), along with 12 BAs, including taurocholic acid (P = 0.02) and tauroursodeoxycholic acid (P = 0.04). Frequencies of high-risk SNPs were not significantly different between the intermediate and advanced AMD groups.

This pilot study identifies distinct gut microbiome compositions and metabolomic profiles associated with AMD and its stages, providing preliminary evidence of a potential link between gut microbiota and AMD pathogenesis. To validate these findings and elucidate the underlying mechanisms, future research with larger cohorts and more comprehensive sampling is strongly recommended.