(P19-015-25) Impact of Diet and Gut Microbiome on Nonhuman Primate Models of Age-Related Macular Degeneration

Objectives: Age-related macular degeneration (AMD) is a major cause of blindness in older adults that is influenced by diet, but the impact of the gut microbiome remains understudied. This study aims to investigate gut microbiome compositions among different pathology and diet intervention groups to elucidate their relationship with AMD pathology. The hypothesis of the study is that the presence of drusen in rhesus macaques is associated with increased abundance of pro-inflammatory bacteria, reduced SCFA-producing bacteria, and altered gut microbiome metabolic pathways, which may collectively contribute to inflammation and AMD-like pathology.

Methods: In this study, we compare gut microbiome composition of aged rhesus macaques with (1) soft drusen, (2) punctate dots, and (3) normal eyes to determine the association of gut microbiota with AMD-related phenotypes in NHPs. We additionally fed a cohort of animals with drusen a high-fat/sugar diet (HFSD) over 12 months to compare the impact of diet on the gut microbiota. Retinal phenotypes were ascertained by ophthalmic examination and ocular imaging, and fecal samples were collected for metagenomic sequencing, followed by differential abundance and pathway analyses to compare gut microbial composition.

Results: We found that pro-inflammatory Gammaproteobacteria, particularly Escherichia and Shigella, were enriched in animals with drusen, while short-chain fatty acid-producing Firmicutes were lower in abundance in these animals. HFSD was associated with higher levels of other pro-inflammatory Gammaproteobacteria like Klebsiella, as well as some SCFA-producing species. Microbial pathway analysis indicates upregulation of pathogen adaptation pathways and downregulation of nutrient utilization pathways in animals with AMD-related phenotypes.

Conclusions: Our findings highlight significant microbial differences associated with AMD-like pathologies. The increase of pro-inflammatory bacteria in animals with drusen indicates that these elevated bacteria may contribute to AMD progression. Additionally, elevated Klebsiella in the HFSD group emphasizes the gut-retina axis as a potential target for therapeutic interventions in AMD.

Funding Sources: This project is supported by funding from the National Institutes of Health.