Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization

Yun Li,Bing Jiang,Yedi Zhou,Jingling Zou,Haixiang Zhou,Wei Tan,Bingyan Li,Chun Ding,Qian Huang,Shigeo Yoshida,Zicong Wang,Yuting Cai

doi:10.3389/fmicb.2021.738796

Abstract

PurposeChoroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.MethodsThe feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.ResultsThe gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.ConclusionThe study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.

Highlights

Age-related macular degeneration (AMD) is one of the main causes of vision loss and blindness worldwide, and its incidence has dramatically increased in the population worldwide (Mitchell et al, 2018)
We have previously reported the expression profiles of mRNA and various types of non-coding RNAs in a choroidal neovascularization (CNV) mouse model (Zhang et al, 2019, 2020; Liu et al, 2020) and indicated the importance of inflammatory cytokines and immune cells in AMD pathogenesis
For the β-diversity analysis, principal coordinate analysis (PCoA) was used after a genus selection-based bacterial taxonomy analysis was performed, and significant differences were not observed when the CNV group was compared with the control group (Figure 1E)

Summary

Introduction

Age-related macular degeneration (AMD) is one of the main causes of vision loss and blindness worldwide, and its incidence has dramatically increased in the population worldwide (Mitchell et al, 2018). The presence of choroidal neovascularization (CNV) is the defining feature of wet or neovascular AMD (nAMD), which is one of the two advanced forms of AMD (Patel and Sheth, 2021). As a first-line therapy, intravitreal injection of antivascular endothelial growth factor (VEGF) agents is effective in patients with nAMD because it targets pathological CNV (Kovach et al, 2012; Ferrara and Adamis, 2016). The limitations of anti-VEGF therapy should not be ignored, such as the side effects of the injection (Xi, 2020) and the unsatisfactory duration of the therapeutic effect (Ehlken et al, 2019). Long-term use of anti-VEGF therapy may lead to serious economic burdens, especially in developing countries and regions (Ruiz-Moreno et al, 2021). Thorough investigation of the mechanisms of nAMD pathogenesis beyond VEGF is urgently needed

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