Effect of Lactiplantibacillus plantarum SCS6 on pancreatic oxidative damage in mice with type 2 diabetes based on gut-pancreas axis.

Type 2 diabetes (T2D) is a metabolic disorder closely associated with oxidative stress. In recent years, Lactiplantibacillus plantarum (L. plantarum), a probiotic lactic acid bacterium, has garnered significant attention due to its potent antioxidant properties and has been utilized in mitigating various chronic diseases mediated by oxidative stress. In this study, L. plantarum SCS6 was isolated from traditional Sichuan fermented sausages. We systematically evaluated the effects of different doses of this strain on multiple parameters in type 2 diabetic mice, including body weight changes, blood glucose levels, insulin(INS) secretion, glycated hemoglobin (HbA1c) concentrations, antioxidant enzyme levels, pancreatic histopathology, immunofluorescence expression, and intestinal microbiota composition. Furthermore, we investigated the strain's regulatory mechanisms underlying oxidative stress modulation to elucidate the potential pathways through which L. plantarum ameliorates type 2 diabetes. Experimental results demonstrated that L. plantarum SCS6 intervention alleviated the progressive weight loss, improved hyperglycemia, increased INS levels, reduced HbA1c concentrations, and attenuated oxidative damage. Histopathological and immunofluorescence analyses further confirmed that L. plantarum SCS6 effectively mitigated pancreatic tissue injury and modulated the expression of antioxidant-related proteins. Furthermore, gut microbiome analysis revealed that in the L. plantarum SCS6-treated mice, the Firmicutes/Bacteroidetes ratio was reduced, the abundance of Lachnospiraceae_NK4A136_group decreased, and that of Muribaculaceae_unclassified increased, indicating a shift toward a more balanced intestinal microbial structure. Concurrently, the production of short-chain fatty acids (SCFAs), particularly acetate, propionate, and butyrate, was significantly enhanced. Taken together, L. plantarum SCS6 may activate the Keap1-Nrf2 signaling pathway via the gut-pancreas axis, modulate antioxidant enzyme expression, and concurrently reshape the gut microbiota composition and promote SCFA metabolism, thereby synergistically contributing to glycemic control and amelioration of diabetes-related symptoms. These findings suggest that L. plantarum SCS6 holds promise as a safe and effective functional probiotic agent for the prevention and management of type 2 diabetes.