Alterations of the Gut Microbiome and Metabolome in Patients With Proliferative Diabetic Retinopathy.

Panpan Ye,Yufeng Xu,Ke Yao,Xueyou Zhang,Xiaoxiao Song,Jia Xu

doi:10.3389/fmicb.2021.667632

Abstract

Diabetic retinopathy (DR) has been reported to associate with gut microbiota alterations in murine models and thus “gut-retina-axis” has been proposed. However, the role of gut microbiome and the associated metabolism in DR patients still need to be elucidated. In this study, we collected fecal samples from 45 patients with proliferative diabetic retinopathy (PDR) and 90 matched diabetic patients (1:2 according to age, sex, and duration of diabetes) without DR (NDR) and performed 16S rRNA gene sequencing and untargeted metabolomics. We observed significantly lower bacterial diversity in the PDR group than that in the NDR group. Differential gut bacterial composition was also found, with significant depletion of 22 families (e.g., Coriobacteriaceae, Veillonellaceae, and Streptococcaceae) and enrichment of two families (Burkholderiaceae and Burkholderiales_unclassified) in the PDR group as compared with the NDR group. There were significantly different fecal metabolic features, which were enriched in metabolic pathways such as arachidonic acid and microbial metabolism, between the two groups. Among 36 coabundance metabolite clusters, 11 were positively/negatively contributed to PDR using logistic regression analysis. Fifteen gut microbial families were significantly correlated with the 11 metabolite clusters. Furthermore, a fecal metabolite-based classifier was constructed to distinguish PDR patients from NDR patients accurately. In conclusion, PDR is associated with reduced diversity and altered composition of gut microbiota and specific microbe-metabolite interplay. Our findings help to better understand the disease pathogenesis and provide novel diagnostic and therapeutic targets for PDR.

Highlights

Diabetes mellitus is growing fast and estimated to affect 10.2% (578 million) of the global population in 2030 (Saeedi et al, 2019)
A total of 45 patients receiving operation for Proliferative diabetic retinopathy (PDR) were included. Another 90 propensity score-matched diabetic patients without PDR according to age, gender, and history of diabetes were enrolled as control group
Gut-retina axis has been proposed according to the mice experiments (Floyd and Grant, 2020) and hypothesize that diabetic-associated microbiome could lead to increased inflammation and vascular permeability, which influence the development and progression of Diabetic retinopathy (DR) (Fernandes et al, 2019)

Summary

Introduction

Diabetes mellitus is growing fast and estimated to affect 10.2% (578 million) of the global population in 2030 (Saeedi et al, 2019). Diabetic retinopathy (DR) is its most common microvascular complication and a major cause of the worldwide vision impairment (Duh et al, 2017). Proliferative diabetic retinopathy (PDR) is the advanced stage of DR and the leading cause of blindness. Gut Microbiome and Metabolome in PDR (Duh et al, 2017). Intravitreous injection of antiVEGF drugs, laser, and vitrectomy have been developed to treat PDR. These treatments seem to be effective, some of the treated eyes still deteriorate and lose vision (Duh et al, 2017), necessitating the development of novel therapeutic approaches

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Conclusion