Gut Microbiota Alterations Linked to Diabetic Retinopathy: Systematic Review & Meta-Analysis

Overview

This systematic review and meta-analysis evaluated the relationship between gut microbiota composition and diabetic retinopathy (DR). Findings indicate significant alterations in gut microbial diversity and composition in DR patients compared to diabetic patients without retinopathy and healthy controls, suggesting a potential gut–eye axis in DR pathogenesis.

Background

The human gut microbiota, primarily composed of Firmicutes and Bacteroidetes, plays a crucial role in physiological processes including inflammation regulation and energy balance. Diabetes mellitus (DM), characterized by chronic hyperglycemia, is associated with complications such as diabetic retinopathy, which affects approximately 35% of diabetic individuals. Emerging evidence supports that gut dysbiosis contributes to DR development through mechanisms involving systemic inflammation, oxidative stress, and vascular dysfunction. Understanding the gut microbiota's role offers a novel perspective on modifiable pathways in DR pathogenesis.

Data Highlights

The meta-analysis quantitatively assessed alpha diversity indices (Chao1, ACE, observed OTUs, Shannon, and Simpson) comparing DR patients with DM without retinopathy and healthy controls. Data were pooled using standardized mean differences (SMDs) with random-effects models, incorporating studies primarily from China and India. Robustness was ensured by excluding statistical outliers and performing leave-one-out sensitivity analyses.

Key Findings

• Gut microbiota alpha diversity is significantly altered in patients with diabetic retinopathy compared to diabetic patients without retinopathy and healthy controls.
• Specific microbial taxa shifts, including changes in Firmicutes and Bacteroidetes proportions, are associated with DR severity and progression.
• Gut dysbiosis may exacerbate systemic inflammation, oxidative stress, and vascular permeability, contributing to retinal microvascular damage in DR.
• The gut–eye axis represents a novel modifiable pathway linking diabetes-induced metabolic disturbances to retinal pathology.
• Meta-analytic evidence supports the potential causality of gut microbiota alterations in DR development, although molecular mechanisms require further elucidation.

Clinical Implications

Clinicians should consider the gut microbiota as a potential therapeutic target in managing diabetic retinopathy. Interventions aimed at restoring gut microbial balance may help mitigate systemic inflammation and vascular dysfunction implicated in DR pathogenesis. Future research into microbiota-modulating therapies could provide adjunctive strategies to current glycemic and vascular control measures.

Conclusion

This systematic review and meta-analysis underscore the significant association between gut microbiota alterations and diabetic retinopathy, highlighting the gut–eye axis as a promising area for therapeutic intervention. Further studies are warranted to clarify causal mechanisms and develop microbiota-targeted treatments.

References

1. Global Burden of Disease Study 2020 -- Trends in Diabetic Retinopathy Prevalence
2. World Health Organization 2021 -- Diabetes Mellitus Global Report
3. Recent Meta-Analyses on Gut Microbiota and Diabetes -- Systematic Review 2025