Lactobacillus plantarum HAC01 ameliorates type 2 diabetes in high-fat diet and streptozotocin-induced diabetic mice in association with modulating the gut microbiota

Type 2 diabetes mellitus (T2DM) is a serious metabolic disorder that occurs worldwide; however, this condition can be managed with probiotics. We assessed the potential therapeutic effects of Lactobacillus plantarum HAC01 on hyperglycemia and T2DM and determined their potential mechanisms using mice with high-fat diet (HFD) and streptozotocin (STZ)-induced diabetes. The diabetic model was established with an HFD and 50 mg kg^-1 STZ. L. plantarum HAC01 was then administered for 10 weeks. Body weight, food and water intake, biochemical parameters, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. Oral glucose tolerance test and histological analysis were performed, and the glucose metabolism-related gene expression and signaling pathways in the liver were determined. Fecal microbiota and serum short-chain fatty acids (SCFAs) were also analyzed. L. plantarum HAC01 significantly lowered blood glucose and HbA1c levels and improved glucose tolerance and HOMA-IR. Additionally, it increased the insulin-positive β-cell area in islets and decreased the mRNA expression levels of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, which are associated with gluconeogenesis. L. plantarum HAC01 also increased the phosphorylation of AMPK and Akt, which are involved in glucose metabolism in the liver. Notably, L. plantarum HAC01 increased the Akkermansiaceae family and increased SCFAs in serum. L. plantarum HAC01 could alleviate hyperglycemia and T2DM by regulating glucose metabolism in the liver, protecting the islet β-cell mass, and restoring the gut microbiota and SCFAs. L. plantarum HAC01 may thus be an effective therapeutic agent for T2DM.