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

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.