The relationship between diabetic retinopathy and intestinal microbiota: a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: Reported as statistically significant for named taxa; specific p-values not available in abstract

• Effect Size: Phylum level — Patescibacteria and Synergistetes: significantly lower abundance in DR vs T2DM; Verrucomicrobia: significantly higher abundance in DR vs T2DM. Genus level — Bacteroides: significantly higher abundance in DR vs T2DM. Quantitative pooled effect sizes (SMD or ratio) not reported in abstract.

• Primary Outcome: Alpha-diversity: no significant difference between T2DM and DR patients. Taxonomic composition: significant differences at phylum and genus levels between DR and T2DM groups

• Nnt Or Sensitivity: Not applicable for this observational microbiome meta-analysis; no NNT, sensitivity, specificity, or hazard ratio calculable from available data

• Confidence Interval: Not reported in available data

Clinical Application

Currently not feasible for clinical translation. Gut microbiota profiling is not a validated diagnostic or prognostic tool for DR in any clinical guideline. The findings are exploratory and require prospective validation in diverse populations before any clinical application can be considered. Microbiome-targeted interventions (probiotics, prebiotics, dietary modification) for DR prevention remain investigational. Diabetic retinopathy affects approximately 1 in 3 Australians with diabetes and is the leading cause of preventable blindness in working-age adults (Diabetes Australia). Current RACGP and Optometry Australia guidelines emphasise glycaemic control (HbA1c targets), blood pressure management, and regular retinal screening as the evidence-based pillars of DR prevention and management. Microbiome-based interventions are not currently recommended by the TGA, PBS-listed, or incorporated into RACGP clinical guidelines. The geographic restriction of this meta-analysis to Chinese and Indian populations limits direct applicability to Australia's diverse multicultural population, though these ethnic groups are well-represented in Australian diabetes cohorts. Any future Australian research should account for the known microbiome-modifying effects of metformin (PBS-listed first-line agent), SGLT2 inhibitors, and GLP-1 receptor agonists — all commonly prescribed in Australian T2DM management — as potential confounders. Adults with established T2DM being evaluated for or diagnosed with diabetic retinopathy. Findings are most directly applicable to East and South Asian populations given the geographic restriction of included studies. Application to other ethnic groups requires substantial caution.

Abstract

PURPOSE: The results of human observational studies on the correlation between gut microbiota and diabetic retinopathy (DR) are discrepant. This meta-analysis aimed to evaluate the specificity of the gut microbiota in DR patients compared to patients with type 2 diabetes mellitus (T2DM). METHODS: All published literature up to October 2024 was searched by two researchers on PubMed, Embase and Web of Science databases. Diversity and gut microbiota composition were the main outcomes. The meta-analysis was conducted in Review Manager (RevMan) Version 5.3. RESULTS: Eight studies, investigating gut microbiota by collecting stool samples, conducted in China and India were included in this meta-analysis, involving a total of 486 individuals in the T2DM (n = 258) and DR (n = 228) groups. No significant difference in alpha-diversity was observed between T2DM and DR patients. The pooled estimate showed that, at the phylum level, the abundances of Patescibacteria, and Synergistetes were significantly lower, and Verrucomicrobia were considerably higher in DR patients than in T2DM patients. At the genus level, DR patients had an increase in Bacteroides compared to T2DM. CONCLUSIONS: In this meta-analysis with a small number of studies and relatively high heterogeneity, changes in gut microbiota were associated with DR, commonly reflected by a reduction in beneficial species and an increase in pathogenic species influencing metabolic pathways.

References

1. 1.Chen, S., Liu, C., Bi, W., Kong, Y., Huang, W., Chen, D., & Leng, Y. (2025). The relationship between diabetic retinopathy and intestinal microbiota: a systematic review and meta-analysis. Diabetes Research and Clinical Practice. https://doi.org/10.1016/j.diabres.2025.112346