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. 2025 Jul 22:18:2451-2462.
doi: 10.2147/DMSO.S527069. eCollection 2025.

Characterization of Vitreous Microbiota Dysbiosis Associated with Proliferative Diabetic Retinopathy

Fangying Song  1 , Yan Qi  1 , Wenhui Ma  1 , Jun Li  1 , Yan Gao  1 , Xiubin Ma  1   2
Affiliations

Characterization of Vitreous Microbiota Dysbiosis Associated with Proliferative Diabetic Retinopathy

Fangying Song et al. Diabetes Metab Syndr Obes. .

Abstract

Purpose: Emerging evidence suggests an association between ocular microbiota dysbiosis and ophthalmic diseases; however, the role of the posterior segment microbiome in diabetic retinopathy (DR) remains poorly characterized. In this study, we characterized the vitreous microbiome of patients with proliferative diabetic retinopathy (PDR) and systematically compared its microbial community structure with that of healthy controls.

Methods: A cohort of 19 PDR patients with type 2 diabetes mellitus and 19 non-DR controls were enrolled, with vitreous samples obtained through vitrectomy. Vitreous microbial composition was characterized using 2bRAD-M sequencing technology, enabling species-level taxonomic resolution. The comparison of dominant taxa, biomarker analysis and metabolic pathway differences between the two groups were further explored.

Results: The results of microbiome profiling revealed significant compositional differences in the vitreous core microbiome of PDR patients compared to controls, potentially associated with enhanced activity in membrane transport, nucleotide metabolism and carbohydrate metabolism pathways. LEfSe analysis identified 536 distinctive biomarkers of the two groups. At species level, the PDR group had significantly lower relative abundances of CAG-485_sp009775375, Akkermansia_muciniphila and Bacteroides_acidifaciens, compared with control group.

Conclusion: This is the first study confirming the microbiota in human vitreous fluid samples by 2bRAD-M sequencing. These findings suggest a potential link between vitreous microbial dysbiosis and PDR, offering novel insights for future mechanistic investigations into DR.

Keywords: 2bRAD-M; microbiota; proliferative diabetic retinopathy; vitreous fluid.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic illustration of the study.
Figure 2
Figure 2
Vitreous microbial diversity of PDR and control groups. (A) Venn diagram of overlapping species between the two groups. (B) Alpha diversity comparison between the two groups via Chao1, Shannon index, and Simpson index analysis. (C) Beta diversity comparison between the two groups based on 3D‑PCoA analysis. Bray–Curtis distance, Binary Jaccard distance and Euclidean distance metrics were used. Each point in the plot represents a sample.
Figure 3
Figure 3
Vitreous microbial community composition. Relative abundance of the top 30 phyla (A) genus (B) and species (C) in the two groups.
Figure 4
Figure 4
LEfSe analysis of differential abundances of microbial taxa between the two groups. (A) Cladogram of taxonomic hierarchical structure biomarkers of the two groups. (B) Differential species score plots present the species with relatively high abundance in each of the two groups.
Figure 5
Figure 5
Results of KEGG function prediction for the top 10 most significant differences.
Figure 6
Figure 6
Heatmap of Spearman correlation analysis of the top 30 relative abundance species and top 30 differential KEGG pathways (P-values: * 0.01–0.05, ** 0.01–0.001; *** < 0.001).
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