Probiotic Supplement Use and Diabetic Retinopathy in Korean Adults with Diabetes: A Nationwide Population-Based Study

Background/Objectives: Experimental studies implicate the gut microbiome in diabetic retinopathy (DR), but population-based data on probiotic supplementation and DR are lacking. We examined this association in Korean adults with diabetes. Methods: We analyzed 2071 adults with diabetes in the Korea National Health and Nutrition Examination Survey 2018–2021 with graded fundus photographs and a product-level dietary supplement interview. We used survey-weighted logistic regression (prespecified) and Poisson regression (added after the initial analysis) estimated odds ratios (ORs) and prevalence ratios (PRs), adjusted for age, sex, hypertension, smoking, and household income (Model 1), and additionally for diabetes duration and glycated hemoglobin (HbA1c) (Model 2, primary), with further adjustment for clinical, lifestyle, and dietary factors. Results: Probiotic supplements were used by 10.4% of participants. Weighted DR prevalence was 11.0% among users and 21.1% among non-users (Model 2 PR 0.57, 95% CI 0.36–0.90; OR 0.49, 95% CI 0.28–0.86; 27 exposed cases; fully adjusted PR 0.59, 95% CI 0.37–0.95). In exploratory analyses, compared with non-use, the PRs were 0.76 (95% CI 0.45–1.29; not statistically significant) for use of <1 year and 0.28 (95% CI 0.13–0.62) for use of ≥1 year. No probiotic user had vision-threatening DR, compared with 3.9% of non-users (unadjusted design-based p = 0.024), a descriptive observation that does not demonstrate a protective effect. Use of any non-probiotic supplement was not associated with DR (PR 0.92), although vitamin C and vitamin A/lutein supplements showed inverse associations of similar magnitude. Conclusions: Probiotic supplement use was associated with a lower prevalence of DR among Korean adults with diabetes. These cross-sectional findings are consistent with, but do not establish, a role of the gut–retina axis in DR and require confirmation in prospective studies.