| The incidence of type ? diabetes(T2D)in the world was ever-increasing.Probiotics played an effective regulatory role in the improvement of T2 D.Previous results showed that Lactobacillus paracasei subsp.Paracasei G15 and Lactobacillus casei Q14,which were isolated from the traditional fermented food,had potential role for prevetion T2 D,And their mechanisms were closely related to intestinal flora.In this study,the mechanism of anti-diabetic effect of Lactobacillus G15 and Q14 was explored basing on the intestinal flora as the core.Diabetic group models were established using a HFD for 6 weeks and followed by a low-dose STZ injection according to the previous studies.Five groups(n=8 each)were identified as follows: Normal control group(N),Diabetes control group(D),Metformin treated group(M),Lactobacillus G15 treated group(G),Lactobacillus Q14 treated group(Q).After 13 weeks of animal experiment,the serum samples were determined by ELISA,the intestinal flora,short chain fatty acid receptor,tight junction protein and inflammatory factors were determined by RT-PCR.Gas chromatography Method were applied for the analysis of short-chain fatty acids(SCFAs),immunohistochemistry and HE staining were used for the analysis of intestinal permeability and barrier function.G15 and Q14 significantly improved body weight,glucose tolerance,insulin resistance and the level of blood lipid in T2 D rats.The treatment of G15 and Q14 significantly improved the loss of body weight.After a 6-week treatment with G15 and Q14,glucose tolerance in the treatment group was significantly higher than that in the model group,and G15 and Q14 treatment also significantly improved the increase of insulin and glucagon in T2 D,G15 and Q14 ameliorated the damaged symptoms of islet beta cells.Additionally,G15 and Q14 also alleviated the increase of lipid level.Lactobacillus G15 and Q14 played the role in T2 D by influencing the gut bacteria-SCFAs-G protein coupled receptor(GPRs)pathway.Results showed that G15 and Q14 enriched the contents of SCFA-producing bacteria(Lactobacillus and Bifidobacterium-mainly produceacetate,Clostridium leptum-mainly produce butyrate,Bacteroides Prevotella-mainly produce acetate and butyrate),and G15 and Q14 upregulated the production of acetate and butyrate,G15 and Q14 further regulated T2 D by the expression of short-chain fatty acid receptor 43(GPR43)and its downstream secreted hormone(GLP-1,PYY),G15 and Q14 increased the expression of GPR43 and the secretion of GLP-1 and PYY.Lactobacillus G15 and Q14 played the role in T2 D by influencing the intestinal mucosal structure,tight junction proteins system,mucosal permeability and inflammatory index.G15 and Q14 significantly reduced the levels of Gram-negative bacteria(G-),Bacteroides and Enterobacterium,and accompanied with a decrease in plasma lipopolysaccharide(LPS)levels in T2 D rats.Histopathological observation showed that the intestinal epithelial cells of diabetic rats colonic tissue were partially damaged,the connection between intestinal epithelial cells was broken,the number of goblet cells decreased,however G15 and Q14 repaired the damage of intestinal mucosal barrier.Immunohistochemical analysis showed that G15 and Q14 significantly improved the expression of tight junction proteins(ZO-1,Occludin and Muc2).G15 and Q14 further reduced the levels of IL-1?,IL-6 and IL-8 in T2 D rats.Taken together,Lactobacillus G15 and Q14 improved glucose tolerance and insulin resistance in T2 D rats.The antidiabetic mechanisms as follows:(1)G15 and Q14 regulated T2 D by intestinal flora-SCFA-GPRs pathway.(2)G15 and Q14 reversed the disturbance of intestinal flora,repaired intestinal mucosal barrier damage,reduced intestinal permeability and consequently inhibited the secretion of inflammatory factors.This study provided a detailed antidiabetic mechanism.The results further confirmed that probiotics from traditional fermented foods have potential antidiabetic effects,which provided an insight in prevetion T2D. |
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