The role of probiotics in modulating the gut microbiota as a potential inhibitor of diabetic kidney disease progression

INTRODUCTION: Gut dysbiosis is commonly observed in patients with diabetic kidney disease (DKD) and may contribute to its pathogenesis. Among microbial metabolites, butyrate plays a key role in regulating antioxidant proteins in type 2 diabetes mellitus (T2DM). Based on this, we hypothesized that the administering probiotics to diabetic rats modulates redox status and thereby attenuates renal disease progression. METHODS: An in vivo study was performed using 15 male Wistar rats (8 weeks old, 250-300 g) randomized into three groups (n = 5/group): Control (vehicles: 0.9% saline and 0.1 M citrate, pH 4.2, i.p., on day 1), T2DM (nicotinamide 100 mg/kg, i.p., followed by streptozotocin 60 mg/kg, i.p., in 0.1 M citrate buffer, pH 4.2), and T2DM + Prob (T2DM protocol plus a multistrain probiotic-Bifidobacterium longum, Bifidobacterium bifidum, and Lactobacillus rhamnosus-1010 CFU/mL by gavage for 6 weeks). The parameters evaluated were: serum creatinine, inulin clearance, microalbuminuria, urinary and lipid peroxides, glutathione, and nuclear factor erythroid 2-related factor 2 (Nrf2). RESULTS: Probiotic treatment significantly increased Nrf2 expression and glutathione levels, reduced urinary and lipid peroxidation, and-beyond attenuating oxidative stress-improved renal function, with lower serum creatinine and microalbuminuria and higher inulin clearance. CONCLUSION: These findings indicate that probiotics prevented DKD progression, likely by modulating oxidative stress via the gut microbiota. These results suggest that probiotics may serve as renoprotective agents, potentially reducing DKD morbidity in T2DM.