Lactobacilli G15 And Q14 Alleviates Type 2 Diabetes In Association With Regulation Of Gut Microbiota In Rats

The ever-increasing prevalence of type 2 diabetes(T2D) has been one of the biggest health challenges in the world. Compelling evidence supports that the intestinal microbiome is important in the pathophysiology of T2 D. Therefore, targeting and controlling the gut microbiota has been viewed as a novel strategy to prevent even cure T2 D. The aim of this study was to investigate the antidiabetic effect of oral administration of Lactobacillus. paracasei subsp. paracasei G15 and Lactobacillus. casei Q14 on the high fat diet and streptozotocin-induced type 2 diabetic rats. The strains were separated from Chinese traditional diary food by our lab previously. This study focus on the involvement of G15 and Q14 in the prognosis management of T2 D, and elucidation of key mechanisms associated with gut microbiota.Pre-screening of antidiabetic lactobacillus by glucose-stimulated insulin secretion test. Lactobacillus G15 and Q14 significantly promoted insulin secretion of the glucosestimulated INS-1 cells, respectively 59.41% and 47.96% compared with the control(P<0.01). The strains also exhibited good tolerance to gastric acid and intestinal fluid. The viability was 58.5% and 64.9%(5.68 and 6.22 log cfu·m L-1)respectively after exposure to gastric acid for 3 h, and 84.6% and 90.8%(8.06 and 8.40 log cfu·mL-1)respectively after exposure to intestinal fluid for 3 h. The results implied their potential as a functional supplement for improvement of T2 D.Lactobacillus G15 and Q14 improved the glycemic control. G15 and Q14 treatment significantly improved the glucose tolerance(P<0.0001) and reduced the HbA1 c levels(P<0.0001) in T2 D rats. G15 and Q14 also reversed the weight loss induced by T2 D, and the probiotics in combination with metformin exerted better efficacy than given alone(P<0.05).Lactobacillus G15 and Q14 alleviated dysbiosis and elevated intestinal permeability: G15 and Q14 could balance the intestinal microecology which appeared to be beneficial for T2 D rats, as they promoted a healthier intestinal microenvironment through modification of the gut microbiota(by PCR-DGGE-PCA analysis), which in turn reduced the intestinal mucosal permeability and improved epithelial barrier function(by colonic histopathologic evaluation). The strains reduced plasma LPS level of T2 D rats(P<0.01), alleviated the metabolic endotoxemia.The probiotic treatments lowered circulating inflammation cytokines, including IL-1β(P<0.01) and IL-8(P<0.001), eventually alleviated inflammatory status and islet β-cells dysfunction. The histological abnormalities of pancreatic islets were also effectively reversed. Administration in combination of Metformin, Lactobacillus Q14 reversed the thymic atrophy and both Lactobacillus G15 and Q14 lowered the circulating IL-6 level, indicating an immune-modulating potential of the strains.Taken together, L. paracasei subp. paracasei G15 and L. casei Q14 improved the glucose intolerance and reduced the HbA1 c levels in T2 D rats. They also reduced intestinal mucosal permeability and improved epithelial barrier function through modification of the gut microbiota, and eventually lowered circulating LPS and alleviated T2D-associated inflammation. L. paracasei subp. paracasei G15 and L. casei Q14 exhibit good antidiabetic effect(type 2), which provided an insight for the biotherapy potential of traditional fermented food for the treatment of diabetes.