The gut microbiome in advanced age-related macular degeneration

Abstract

Purpose : Genetic risk factors for age-related macular degeneration (AMD) and the benefit of oral vitamin supplementation in slowing AMD progression are well-established. The link between the gut and AMD is not well understood but innate immune system defense against bacterial pathogens has been implicated in AMD pathogenesis. We performed a case-control observational study to test the hypothesis that alterations in the gut microbiota in AMD affect pathways involved in the pathogenesis of AMD.

Methods : Case control study. Subjects with AMD and controls answered a questionnaire regarding health history with focus on inflammatory/autoimmune conditions, diet, medications, family history and allergies and provided stool and/or serum samples. Gut microbial composition was determined by DNA extraction from stool samples, PCR amplification of 16s DNA and gene sequencing using Illumina MiSeq. DNA sequences were grouped into operational taxonomic units (OTUs) at 97% similarity. Functional potential was inferred using Piphillin and Kyoto Encyclopedia of Genes and Genomes (KEGG) to identify metabolic pathways inferred by the constituent bacteria (97% identity cutoff). Subjects underwent genotyping for 25 genes/loci implicated in AMD.

Results : There were 85 subjects with AMD (mean age 82.5 years, 36% male, number obese 26.1, 60% with >=1 comorbidity) and 49 controls (mean age 76.4 years [p <0.0001], 47% male [p = 0.23], 27.6 obese [p=0.57], 43% >=1 comorbidity [p=0.06]). Of cases, the identified CFH rs1061170 CC risk allele was present in 36.8% (14.7% of controls [p=0.02]), and the ARMS2 rs10490924 TT risk allele was present in 23.7% (2.9% of controls [p=0.008]). 72 metabolic pathways were represented by gut microbiota with significant differences identified using DeSeq2 (p<0.05, adjusted for multiple comparisons metabolic pathways). These were enriched for lipid metabolism, metabolism of terpenoids and polyketides, and cellular processes in both AMD and control; for xenobiotics degradation and human diseases in AMD; and for organismal systems in controls (Figure).

Conclusions : Gut bacteria enriched in patients with AMD versus controls implicate differential functions in pathways for lipid and drug metabolism, carotenoid biosynthesis, bacterial chemotaxis and cell death suggesting that the gut microbiota may affect the pathogenesis of AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Metabolic pathways represented by gut microbial constituents, enriched in controls and in AMD