Retinal artery occlusion is associated with compositional and functional shifts in the gut microbiome and altered trimethylamine-N-oxide levels

Denise C Zysset-Burri,Lieselotte E Berger,Irene Keller,Sebastian Wolf,Martin S Zinkernagel,Christian Steuer,Peter J Neyer

doi:10.1038/s41598-019-51698-5

Abstract

Retinal artery occlusion (RAO) is a sight threatening complication of cardiovascular disease and commonly occurs due to underlying atherosclerosis. As cardiovascular disease and atherosclerosis in particular has been associated with compositional alterations in the gut microbiome, we investigated this association in patients with clinically confirmed non-arteritic RAO compared to age- and sex-matched controls. On the phylum level, the relative abundance of Bacteroidetes was decreased in patients with RAO compared to controls, whereas the opposite applied for the phylum of Proteobacteria. Several genera and species such as Actinobacter, Bifidobacterium spp., Bacteroides stercoris, Faecalibacterium prausnitzii were relatively enriched in patients with RAO, whereas others such as Odoribacter, Parasutterella or Lachnospiraceae were significantly lower. Patient’s gut microbiomes were enriched in genes of the cholesterol metabolism pathway. The gut derived, pro-atherogenic metabolite trimethylamine-N-oxide (TMAO) was significantly higher in patients with RAO compared to controls (p = 0.023) and a negative correlation between relative abundances of genera Parasutterella and Lachnospiraceae and TMAO levels and a positive correlation between relative abundance of genus Akkermansia and TMAO levels was found in study subjects. Our findings proposes that RAO is associated with alterations in the gut microbiome and with elevated TMAO levels, suggesting that RAO could be targeted by microbiome-altering interventions.

Highlights

Retinal artery occlusion (RAO) is a sight threatening complication of cardiovascular disease and commonly occurs due to underlying atherosclerosis
Diet has been identified as the major risk factor for cardiovascular disease with a positive correlation with total and low-density lipoprotein (LDL) cholesterol and an inverse correlation with high-density lipoprotein (HDL) cholesterol[4,5]
Links between the gut microbiome and diabetes mellitus and obesity have been revealed in the last decade, both of which are associated with atherosclerosis[11,12,13]

Summary

Introduction

Retinal artery occlusion (RAO) is a sight threatening complication of cardiovascular disease and commonly occurs due to underlying atherosclerosis. In retinal diseases such as age related macular degeneration, which is the leading cause of irreversible severe visual loss in the western world and has been associated with atherosclerosis[14], alterations in the gut microbiota have been described[15,16]. Dysbiosis in the gut has been shown to lead to increased permeability of the intestine, which in turn causes increased systemic levels of bacterial products resulting in low-grade chronic inflammation[18]. This may directly affect atherogenesis and may lead to the development of insulin resistance with concomitant effects on plasma lipids[19]. We performed a systematic analysis of the gut microbiome and associated metabolic pathways and analyzed TMAO levels as well as genes of the TMAO synthesis pathway in patients with symptomatic RAO and controls

Methods

Results

Conclusion