The beneficial effects of the composite probiotics from camel milk on glucose and lipid metabolism, liver and renal function and gut microbiota in db/db mice.

BACKGROUND: Probiotics may have beneficial effects on patients with type 2 diabetes mellitus (T2DM). We separated 4 lactobacillus and 1 saccharomycetes from traditional fermented cheese whey (TFCW) and prepared composite probiotics from camel milk (CPCM) and investigated their effects on glucose and lipid metabolism, liver and renal function and gut microbiota in db/db mice. METHODS: CPCM was prepared in the laboratory and 40 db/db mice were randomly divided into 4 groups as metformin, low-dose and high-dose group and model group, and treated for 6 weeks. In addition, 10 C57BL/Ks mice as normal control group were used for comparison. Fasting blood glucose (FBG), body weight (BW), oral glucose tolerance test (OGTT), glycated hemoglobin (HbAlc), C-peptide (CP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), 24 h urinary microalbumin (24 h malb), urine ketone, urine sugar, pancreas and liver tissue and intestinal flora were tested. RESULTS: Compared to diabetic group, high dose CPCM significantly decreased FBG, OGTT, HbAlc and IRI, plasma TC, TG, LDL-C, 24 h malb, urine ketone and urine sugar, increased CP, HDL-C levels, improved the liver and kidney function, protected the function of islets, also increased intestinal tract lactic acid bacteria and Bifidobacterium, decreased Escherichia in db/db mice. CONCLUSION: CPCM decreased FBG, OGTT and HbAlc, increased CP, modulated lipid metabolism and improved liver and kidney protected injury in db/db mice, which may be related to various probiotics acting through protecting the function of islets and regulating intestinal flora disturbance.

Fourteen composite probiotics alleviate type 2 diabetes through modulating gut microbiota and modifying M1/M2 phenotype macrophage in db/db mice.

Dysregulation of intestinal microbiota accelerates the development of type 2 diabetes. Probiotics are potential adjunctive therapy in the treatment of diabetes. This study investigated the anti-diabetic mechanism of 14 composite probiotics. Results showed that treatment with 14 composite probiotics improved intestinal microbiota equilibrium by increasing the population of short-chain fatty acids (SCFAs)-producing bacteria and decreasing the number of harmful bacteria. Further, the probiotics significantly improved blood glucose metabolism by promoting glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion. These effects were ascribed to the activation of GPR43/41, restoration of the pancreatic structure, the elevation of insulin secretion and balancing of blood glucose-related parameters. Additionally, the 14 composite probiotics markedly restored gut barrier function via activating antioxidant enzymes, promoting tight junction protein expression, inhibiting the activity of pro-inflammatory factors and improving the morphology of the colon. Furthermore, the 14 composite probiotics upregulated M2 polarization factors and downregulated M1 polarization factors, possibly through TLRs/MyD88/NF-κB signaling pathway. These results indicate that the 14 composite probiotics can potentially improve diabetes prognosis.

Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP-1 secretion in db/db mice.

BACKGROUD/AIM: Previous studies have found that probiotic fermented camel milk has anti-diabetic effect by inducing (glucagon-like peptide-1) GLP-1 secretion. Probiotics are valuable in prevention and treatment of diabetes. As a result, our team islolated 14 probiotics from fermented camel milk. These probiotics have beneficial characteristics, but the possible anti-diabetic mechanisms remains unclear. The present study aimed to explore the possoble anti-diabetic mechanisms of 14 probiotics. METHODS: C57BL/Ks mice were normal group. The db/db mice were randomized into five groups: model group, metformin group, liraglutide group, low-dose and high-dose probiotic group. Biochemical parameters were determined by the respective assay kits. The levels of the short-chain fatty acids (SCFAs) and microbiota were respectively determined by gas chromatography and qRT-PCR. HE staining and immunofluorescence were used for histomorphological observation. Quantitative PCR and western-blot were determined the gene and protein expression of Bax, Bcl-2, Caspase-3 and PI3K/AKT. RESULTS: Probiotics significantly improved blood glucose and blood lipid parameters, as well as the morphological changes of pancreas, liver and kidney. Probiotics improved the gut barrier function through increasing the levels of SCFA-producing bacteria and SCFAs as well as the expression of claudin-1 and mucin-2, and decreasing Escherichia coli and LPS level. In additon, probiotics enhanced insulin secretion through glucose-triggered GLP-1 secretion by upregulating G protein-coupled receptor 43/41 (GPR43/41), proglucagon and proconvertase 1/3 activity. Forthermore, probiotics protected pancreas against apoptosis, which may be dependent on the upregulation of PI3K/AKT pathway. CONCLUSIONS: The anti-diabetic effect of 14 probiotics in db/db mice seem to be related to an increase of SCFA-producing bacteria, the improvement of intestinal barrier function and the upregulation of GLP-1 production, and indicate these probiotics might be a good candidate to prevent and treat diabetes.

Anti-atherosclerotic effect of traditional fermented cheese whey in atherosclerotic rabbits and identification of probiotics.

BACKGROUND: Traditional fermented cheese whey (TFCW), containing probiotics, has been used both as a dairy food with ethnic flavor and a medicine for cardiovascular disease, especially regulating blood lipid among Kazakh. We therefore investigated anti-atherosclerotic effects of TFCW in atherosclerotic rabbits and identified lactic acid bacteria (LAB) and yeasts in TFCW. METHODS: Atherosclerotic rabbits were induced by administration of atherosclerotic diet for 12 weeks and divided randomly into three groups and treated for 4 weeks with Simvastatin (20 mg/kg) or TFCW (25 mg/kg) and (50 mg/kg). In addition, a normal control group and an atherosclerotic group were used for comparison. All drugs were intragastrical administered once daily 10 mL/kg for 4 weeks. Body weight (BW), lipid profiles, C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were tested and theromatous plaques and the number of foam cells and infiltrating fibroblast cells in the thoracic aorta endothelium was evaluated by hematoxylin and eosin stainin. LAB and yeasts were isolated and purified by conventional techniques and identified using morphological and biochemical properties as well as gene sequences analysis. RESULTS: After 4 weeks of treatment, high and low dose TFCW decreased serum TC, TG, LDLC, CRP, VCAM-1 and ICAM-1 (P < 0.05) compared to atherosclerotic group, and increased HDL-C (P < 0.05) compared to normal controls. Histological analysis showed TFCW reduced VCAM-1 expression and formation of atheromatous plaques on the aortic endothelium of atherosclerotic rabbits. CONCLUSION: Seven classes of LBA from two different genera including Lactobacillus brevis, Lactobacillus kefianofaciens, Lactobacillus helveticus, Lactobacillus Casei, Lactobacillus plantarum, Lactobacillus kefiri and Lactococcus lactic as well as 2 classes of yeasts from two different genera including Saccharomyces unisporus and Issatchenkia orientalis were isolated and identified from TFCW. In summary, TFCW, containing 7 classes of LBA and 2 classes of yeasts, has significant anti-atherosclerotic potential in atherosclerotic rabbits and may modulate lipid metabolism and protect aorta in the atherosclerotic condition, which might be related to various probiotics acting through reducing the CRP, VCAM-1 and ICAM-1 levels and protecting the aortic endothelium.

Anti-diabetic effects of shubat in type 2 diabetic rats induced by combination of high-glucose-fat diet and low-dose streptozotocin.

ETHNOPHARMACOLOGICAL RELEVANCE: Shubat, probiotic fermented camel milk, has been used both as a drink with ethnic flavor and a medicine among Kazakh population for diabetic patients. Kazakh people have lower diabetic prevalence and impaired fasting glucose (IFG) than do other ethnic groups living in Xinjiang China, which might be related to the beneficial properties of shubat. We therefore prepared shubat in laboratory and tested anti-diabetic activity and evaluated its possible hypolipidemic and renoprotective effects in type 2 diabetic rats. MATERIALS AND METHODS: Type 2 diabetic rats were induced by an administration of high-glucose-fat diet for 6 weeks and an intraperitoneal injection of streptozotocin (STZ, 30mg/kg). Diabetic rats were divided randomly into four groups and treated for 28 days with sitagliptin (30mg/kg) or shubat (6.97×10(6) lactic acid bacteria+2.20×10(4) yeasts) CFU/mL, (6.97×10(7) lactic acid bacteria+2.20×10(5) yeasts) CFU/mL and (6.97×10(8) lactic acid bacteria+2.20×10(6) yeasts) CFU/mL. In addition, a normal control group and a diabetic control group were used for comparison. All drugs were given orally once daily 10mL/kg for 4 weeks. Fasting blood glucose (FBG) and body weight (BW) were measured before treatment and every week thereafter. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), serum creatinine (SCr), blood urea nitrogen (BUN), C-peptide, glycated hemoglobin (HbAlc), glucagon-like peptide-1 (GLP-1) levels and pancreas tissue sections were tested after 4 weeks. RESULTS: Shubat demonstrated positive hypoglycemic activity on FBG, HbAlc, C-peptide and GLP-1 levels, high dose shubat decreased FBG (P<0.01) and HbAlc (P<0.05), increased C-peptide (P<0.05) and GLP-1 (P<0.01), decreased serum TC, TG, LDL-c (P<0.05), increased HDL-c (P<0.01), and improved the reduction of body weight as well as decreased SCr and BUN levels (P<0.01) compared to diabetic controls. Histological analysis showed shubat protected the function of islets of type 2 diabetic rats. CONCLUSION: The results of this study indicate that shubat has significant hypoglycemic potential in T2D rats and may modulate lipid metabolism and protect renal function in the type 2 diabetic condition, which might be related to various probiotics acting through promoting the release of GLP-1 and improving the function of ß-cells.