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

Abstract Background: 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. Results: Fecal samples from 45 patients with proliferative DR (PDR) and 90 matched diabetic patients (1:2 according to age, sex and duration of diabetes) without DR (NDR) were subjected to 16S rRNA gene sequencing and untargeted metabolomics. Significantly lower bacterial diversity was observed in PDR group than that in NDR group. Differential gut bacterial composition was found, with significant depletion of 22 families (e.g., Coriobacteriaceae, Veillonellaceae and Streptococcaceae) and enrichment of 2 families (Burkholderiaceae and Burkholderiales_unclassified) in PDR group as compared to 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 co-abundance 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 metabolites-based classifier was constructed to distinguish PDR patients from NDR patients accurately.Conclusions: 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 biomarkers and therapeutic targets for PDR.