| Type 2 diabetes as a common metabolic syndrome is a serious threat to human health.Partial of lactic acid bacteria(LAB)can make beneficial changes in the body's intestinal microecology,effectively reducing blood glucose and lipid levels.As one of the strains of LAB,Enterococcus plays an important role on the physiological statue of host,however,its probiotic properties of hypoglycemic and lipid-lowering effects are rarely known yet at home and abroad,and the mechanism should be investigated.The dissertation is aimed at analyzing the effects of Enterococcus hirae WEHI01on type 2 diabetes,and further exploring its hypoglycemic and lipid-lowering mechanism.The whole study is described in four chapters.In Chapter 1,an overview of the profiles of type II diabetes mellitus(T2DM)and probiotics was presented.For type 2 diabetes,the classification,pathogenesis,prevention and cure were summarized.For probiotics,its functional and the relationship between flora and type 2 diabetes,the biological characteristics,taxonomic status,application,and the relationship between Enterococcus and type 2diabetes were described.The perspective for research and development of enterococci is also proposed.In Chapter 2,the effects of E.hirae WEHI01 on metabolism and intestinal microflora in rats fed high-fat and high-sugar diets were approached.SD rats were randomly divided into three groups,namely,normal group(NC):normal diet;high-fat high-sugar group(HFS):high-fat high-sugar diet;prevention group(HFS-WEHI01):high-fat high-sugar diet+E.hirae WEHI01(5×10~9 cfu/mL/day).The results showed that E.hirae WEHI01 effectively reduced serum levels of TC,LDL-C and HDL-C in rats with high-fat and high-glucose diet,and thus promoted the metabolism of cholesterol.WEHI01 down-regulated the pro-inflammatory cytokines TNF-?,therefore,it has the potential to reduce inflammation.WHI01 down-regulated Crtc2,thereby reducing blood glucose levels;and down-regulated the glycolytic pathway genes ChREBP and GKRP,thereby promoting glucose metabolism.On the other hand,WEHI01 upregulated PPAR-?,regulating the expression of lipid-producing genes,inhibiting NF-kB activity and thus lowing TNF-?expression.WEHI01 upregulated CYP7A1,thereby accelerating cholesterol breakdown;and downregulated FMO3,undoing negative feedback regulation of CYP7A1 gene to accelerate the decomposition of cholesterol;upregulated LDL-R and therefore increasing serum LDL-R clearance.In addition,16S rRNA gene high-throughput sequencing analysis showed that E.hirae WEHI01 can improve the structure of intestinal flora in rats with high-fat and high-sugar diets,increasing the proportion of Bacteroidetes,and reducing the proportion of Firmicutes.In Chapter 3,the effects of E.hirae WEHI01 on body weight,blood glucose,inflammation,histopathology and intestinal flora in T2DM rats were approached.SD rats were randomly divided into three groups,namely,normal group(NDM):normal diet;type 2 diabetes group(DM):high fat and high sugar diet+STZ injection;prevention group(WEHI01):high fat and high sugar diet+STZ injection+E.hirae WEHI01(5×10~9 cfu/mL/day).The results showed that E.hirae WEHI01 effectively increased body weight,reduced blood glucose after STZ modeling,regulated bile acid metabolism,reduced serum levels of inflammatory cytokines TNF-?,IL-6 and IL-10.WEHI01 had protective effect in pancreas,kidney and liver,and significantly improved the structure of intestinal flora via changing the diversity of flora and regulating the proportion of bacteria in diabetic rats.In Chapter 4,effects of E.hirae WEHI01 on high-fat-sugar obese rats and type2 diabetic rats were summarized,and the mechanism of the metabolic pathway and flora substitution were prospected.In summary,E.hirae WEHI01 regulated the metabolic patterns of obesity and type 2 diabetes model by regulating the intestinal flora.The results of this study provide scientific basis for the improvement of type 2 diabetes by using probiotic preparation. |
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