The Alleviating Effect And Mechanism Of Bifidobacterium Adolescentis On Obesity Induced By A High-Fat Diet

Obesity is a chronic metabolic disease characterized by excessive accumulation or abnormal distribution of fat caused by many factors.It is well known that obesity incidence has risen rapidly in recent years and has become a global health and economic burden.Overweight and obesity have continued to grow over the past 40 years,with serious health consequences.What causes obesity and overweight? Excluding pathological factors,the disorder of energy metabolism is the main cause.Long-term intake of high-energy foods and low energy consumption can lead to fat accumulation and white adipose tissue hyperplasia,and change the gut microbiota.Human and animal studies have shown that probiotic supplementation can be used as a means of remodeling gut microbiota to repair gut microbiota imbalance and play a role in alleviating obesity.Previous studies have shown that Bifidobacterium adolescentis can regulate immunity and play a role in relieving metabolic diseases such as diabetes and non-alcoholic fatty liver.Based on the above research background,taking Bifidobacterium adolescentis as the starting point,this study explores the mechanisms of Bifidobacterium adolescentis in relieving obesity caused by a high-fat diet via animal experiments,genomics,and chromatographic analysis,and so on.The main results and conclusions of this study are as follows:(1)High fat diet(HFD)caused obesity and impaired blood glucose homeostasis in mice,and increased the levels of total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and alanine aminotransferase(ALT)in serum.Compared with the low-fat diet,the high-fat diet increased the basal metabolic rate,increased thermogenesis,activated the thermogenic genes in brown adipose tissue,increased the expression of genes related to lipid synthesis and lipolysis in the liver.The HFD increased the biodiversity of cecal and colonic microbiota,increased the abundance of bacteria such as Desulfovibrionaceae(enhanced energy intake),Muribaculaceae(rich in carbohydrate enzymes),Alistipes(metabolic diseases),and Mucispirillum(colitis),and decreased the abundance of beneficial bacteria such as Bifidobacterium,Lactobacillus,Faecalibaculum,Akkermansia and so on.The HFD increased the levels of short-chain fatty acids in cecal and colonic contents,significantly increased the concentrations of propionic acid,isobutyric acid,butyric acid,isovaleric acid,and valeric acid in cecal contents of mice,and increased the concentration of acetic acid in colonic contents.(2)Due to obesity caused by a high-fat diet and the loss of intestinal beneficial bacteria,five strains of B.adolescentis were used to intervene in mice with a high-fat diet.The results showed that different sources of Bifidobacterium adolescentis had different effects on mice fed the HFD,among which B.adolescentis 17?3 from longevous people showed the best effects on improvement of obesity induced by a high-fat diet.B.adolescentis M1 and N4?N3from newborn increased the body weight,weight gain and food intake of mice.B.adolescentis 17?3 decreased the weight gain,abdominal white fat,fasting blood glucose level and maintained blood glucose homeostasis of mice.B.adolescentis 2016?7?2 from the long-lived elderly significantly decreased the respiratory quotient,and 17?3 and Z25 showed the tendency to decrease the respiratory quotient.In addition,B.adolescentis from the long-lived elderly also increased the level of leptin in mice.Supplementation of B.adolescentis changed the composition of gut microbiota in mice with a high-fat diet.B.adolescentis 17?3,N4?N3,and 2016?7?2 decreased the species richness of cecal and colon microbiota in mice,while Z25 and 17?3 increased the evenness of cecal microbiota in mice.B.adolescentis supplementations increased the abundance of Bifidobacterium in the gut microbiota of mice,decreased the abundance of Odoribacter(short and medium-chain fatty acids in production),M1 increased the abundance of Muribaculaceae(producing SCFAs),and17?3 significantly increased the abundance of Akkermansia,which can alleviate obesity and improve blood glucose homeostasis.B.adolescentis also changed the level of intestinal short-chain fatty acids.In the cecum,except for B.adolescentis M1,the other 4 strains decreased the concentration of total short-chain fatty acids,and M1 significantly increased the concentration of acetic acid in the cecum.These 5 B.adolescentis strains decreased the levels of other short-chain fatty acids in varying degrees.In the colon,B.adolescentis 17?3significantly decreased the levels of propionic acid and isobutyric acid,M1 decreased the concentration of isovaleric acid,and 17?3,N4?N3,2016?7?2 decreased the level of valerate.(3)Comparing the effects of different B.adolescentis strains on lipid metabolism,immune regulation,prediction functions of gut microbiota,and ileal bile acid composition of mice fed the high-fat diet,it was found that B.adolescentis 17?3,Z25,and 2016?7?2specifically activated the gene expressions related to non-shivering thermogenesis and lipolysis in brown fat,and significantly up-regulated the expression of Ucp-1,Ppar-?,Ppar-?,Pgc1-?,Hsl,Mgl,and other genes.The results showed that B.adolescentis from the long-lived elderly could increase energy consumption by specifically activating the non-thriller thermogenesis of brown fat and inhibit the excessive accumulation of lipids in mice induced by a high-fat diet.B.adolescentis supplementations can regulate immunity and inhibit tissue inflammation.B.adolescentis inhibited the gene expression of inflammation-related cytokines Il-17 f and Tnf-? in spleen,and increased the gene expression of anti-inflammatory cytokines Foxp3,Il-10 and Il-4,as well as decreased the protein level of pro-inflammatory factors IL-17 and IL-6 in the brain,reduced the gene expressions level of pro-inflammatory factors such as Il-6 and Tlr-4 in hypothalamus,increased the protein level of anti-inflammatory factor IL-10,and increase the gene expression of anti-inflammatory factor Foxp3.The results of prediction functions of gut microbiota showed that B.adolescentis 17?3,Z25 and 2016?7?2 increased the gene abundance of secondary metabolites,antibiotics and amino acid biosynthesis pathways in intestinal flora,and significantly increased the gene abundance of carbohydrate metabolism-related pathways in gut microbiota in HFD group and B.adolescentis N4?N3 intervention group.In addition,B.adolescentis17?3,Z25,and 2016?7?2 increased the proportion of bile acid in the ileum and activated bile acid receptor TGR5 in the ileum.Genomic analysis of B.adolescentis showed that the genomes of B.adolescentis contained mobile genetic elements,which were beneficial to the strains for the adaption of the environment and improving survival competitiveness.The carbohydrate-active enzyme annotation results showed that the carbohydrate esterase and glycoside hydrolase genes of B.adolescentis Z25 were relatively abundant;the comparative genome analysis results showed that there were 8 tunique homologous genes in the B.adolescentis from the elderly and 2 unique homologous genes in the B.adolescentis from the newborns.The effects on alleviating obesity were compared between B.adolescentis 17?3 and other different genera of Lactobacillus and Bifidobacterium probiotics.It was found that different probiotics had different alleviating effects on obese mice,including effects on blood glucose,biochemical indexes,gut microbiota,and short-chain fatty acids in mice.During the intervention of probiotics on obese mice,B.breve 2016?49?7,L.casei 1711,and B.adolescentis 17?3 effectively reduced the weight gain of obese mice,while L.plantarum ZS2058,L.gasseri C1?A31,and B.breve 2016?49?7 significantly reduced the kidney weight of obese mice.The levels of serum alanine aminotransferase and aspartate aminotransferase in obese mice were decreased by B.breve 2016?49?7,L.casei 1711,and B.adolescentis 17?3.The levels of serum HDL-C and LDL-C in obese mice were significantly decreased by B.adolescentis 17?3.The fasting blood glucose of obese mice was significantly decreased by B.adolescentis Z25,17?3and L.casei 1711,and blood glucose homeostasis was improved.The probiotic intervention reduced the biodiversity of cecal microbiota.L.plantarum ZS2058 significantly increased the relative abundance of Bacteroides,and B.adolescentis Z25,17?3and L.plantarum ZS2058 increased the relative abundance of Bifidobacterium in cecum and colon,three strains of Lactobacillus significantly increased the abundance of Lactobacillus in the cecum and colon.B.adolescentis Z25 intervention group and LFD group increased the relative abundance of Ruminococcaceae UCG-014.In addition,probiotic supplementations changed the levels of intestinal short-chain fatty acids.In the cecum,B.brevis 2016?49?7,L.casei 1711,and B.adolescentis 17?3 increased the levels of short-chain fatty acids in cecal contents,including total short-chain fatty acids and 6 kinds of short-chain fatty acids.In the colon,B.brevis 2016?49?7 increased the level of short-chain fatty acids in colon contents,including total short-chain fatty acids.L.casei 1711 significantly increased the levels of propionic acid and valeric acid.