An Association Between the Intestinal Permeability Biomarker Zonulin and the Development of Diabetic Retinopathy in Type 2 Diabetes Mellitus

Abstract

Objectives: Increased intestinal permeability (IP) and gut microbiota dysbiosis have been implicated in low-grade chronic inflammation, which is an important factor in the pathogenesis of diabetic retinopathy (DR). This study aims to demonstrate the relationship between the IP biomarker zonulin and DR in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: This study was conducted with a total of 89 T2DM patients, including 33 non-DR, 28 with nonproliferative DR (NPDR), and 28 with proliferative DR (PDR), and 32 healthy controls. Zonulin levels were determined from blood samples using an enzyme-linked immunosorbent assay kit. Results: There was no difference between the four groups in terms of age (p=0.236), gender (p=0.952), and body mass index (p=0.134) of the participants. Zonulin levels were significantly higher in the PDR group compared to the other three groups, as well as in the non-DR and NPDR groups compared to the control group. In multivariate logistic regression analysis, zonulin was found to be an independent predictor of DR (odds ratio: 1,781, 95% confidence interval: 1,122-2,829, p=0.014). Conclusion: Our study showed that elevated zonulin levels may play a significant role in the development of DR, particularly during the transition to the proliferative stage. This suggests that regulation of IP could be one of the targets of DR treatment. More studies are needed to determine whether a eubiotic gut microbiota and IP have a direct relationship with DR.

Targeting the Gut–Eye Axis: An Emerging Strategy to Face Ocular Diseases

“…Faecal microbiota transplantation (FMT) consists of the transfer of fresh or frozen faecal material from healthy donors to a patient's intestine to restore eubiosis [235]. Although delivery through colonoscopy remains the preferred route, its intrinsic invasiveness and the risks associated with the procedure have recently led to the consideration of enema, nasogastric delivery, or oral pills as alternative transplantation techniques [236,237].…”

Gut Microbiota in Patients with Prediabetes

“…Increased gut permeability promotes low-grade systemic inflammation, which is a root cause for metabolic disorders and various chronic diseases, including type 2 diabetes [8]. These findings are supported by recent studies that found markers such as zonulin and short-chain-fatty-acid-producing bacteria in the gut to have a correlation with diabetes and its complications [8,11]. Thus, investigating the relationship between intestinal bacteria alteration and a compromised gut barrier on the development of diabetes, and the potential factors causing said changes, is imperative to attenuate the progression of prediabetes to diabetes.…”