| Type 2 diabetes(T2D)is a metabolic disease characterized by hyperglycemia.In recent years,the incidence and mortality of T2D has been increasing due to unhealthy factors such as lack of exercise and a high-fat,high-sugar diet.Animal experiments and clinical studies have shown that the abundance of Bifidobacterium in the intestines of individuals with T2D has been reduced,while the intake of Bifidobacterium can relieve T2D.As the predominant Bifidobacterium in the intestines of adults and infants respectively,Bifidobacterium adolescentis(B.adolescentis)and Bifidobacterium bifidum(B.bifidum)have been found to have mitigating effects on metabolic diseases but there are few related studies.The purpose of this paper is to analyze the relief effects on type 2 diabetes which is more common in adults and its pathways by the two species of Bifidobacterium which predominate in different life periods.A high-fat diet and streptozotocin(STZ)were used to establish a model of T2D in mice and 16 strains of human-derived B.adolescentis and B.bifidum were used to intervene T2D mice.The glucose metabolism,blood lipid metabolism and organ lipid accumulation of mice in each group were analyzed to explore the effect on T2D relief by two Bifidobacterium species.The remission pathways for strains to relieve T2D were explored by analyzing the effects on liver oxidative stress indicators,intestinal permeability indicators,inflammation indicators,short chain fatty acids(SCFAs)content and gut microbiota in mice by probiotic intervention.Also,the remission pathways of gut microbiota were predicted using PICRUSt.Besides,the possible mechanisms of the strains to differentially alleviate T2D were preliminarily analyzed at the genetic level by comparing and analyzing the genetic sketch of strains with different remission effects.The main research results are shown as follow:Although the strains failed to improve the insulin secretion,B.bifidum 9M10,B.bifidum 26M7 and 6 strains of B.adolescentis(except for 30M5 and 50M3)were able to reduce islet damage,relieve insulin resistance,reduce fasting blood glucose,reduce abnormally high blood glucose levels caused by oral glucose and alleviate the liver lipid accumulation in T2D mice to vary degrees.Among these 8 strains,B.adolescentis 2016 had the best remission effect,followed by B.adolescentis 8M4、41M3、3M10 and 9M10.B.adolescentis 34M4、26M1 and B.bifidum 26M7 played a certain role.The results of comprehensive analysis indicated that the effects on T2D alleviation by B.adolescentis were better than that by B.bifidum,but the effects on T2D by different strains showed individual differences.We further proceed from the relevant factors involved in the pathophysiological process of T2D to analyze the possible ways of Bifidobacterium to alleviate T2D.It was found that the effects of B.adolescentis on reducing lipid oxidation products,reducing intestinal permeability and increasing species richness of gut microbiota were stronger than those of B.bifidum.Strains with T2D-relieving effect improved inflammation,increased the content of SCFAs and the abundance of SCFAs-producing bacteria such as Bifidobacterium,Ruminococcus,Coprococcus and Roseburia to vary degrees.PICRUSt prediction results of gut microbiota suggested that Bifidobacterium strains with excellent remission effects might regulate pathways such as the ubiquitin system,steroid hormone biosynthesis,steroid biosynthesis and arachidonic acid metabolism pathway to ultimately affect the low-level inflammation.Based on the results of inflammation,SCFAs and gut microbiota,it is speculated that effective Bifidobacterium strains played a role in relieving T2D by increasing the abundance of SCFAs-producing related bacteria,increasing the content of SCFAs and improving the inflammatory state.At the same time,we also analyzed the reasons for different alleviation effects on T2D by different strains from the bacterial genetic level.It was found that the effective strains in B.adolescentis had the glycosyl hydrolase 3 family proteins encoded by the unique genes,and the effective strains in B.bifidum had β-galactosidase encoded by the unique genes.The analysis preliminarily explained the different alleviation effects on T2D by these strains at the genetic level. |
