| With the improvement of living standards,excessive intake of high-fat and high-calorie diets has resulted in a rapid increase in the proportion of overweight and obese people.Obesity is a condition in which excess accumulation of white adipose tissue causes the body to become overweight.According to the content and distribution,body adipose tissue is mainly divided into white adipose tissue and brown adipose tissue.Brown adipose tissue is not only the brown adipose tissue in the body,but also a thermogenic organ that increases the body’s energy release,and has become an important target for the study of the mechanism of obesity treatment.Fecal microbiota transplantation is a method of transplanting functional flora from the feces of a healthy body into the gastrointestinal tract of a patient and remodeling the intestinal microbial environment.In recent years,researchers have found that fecal microbiota transplantation can not only reshape the gut microbial environment and alleviate weight gain in obese patients,but also widely used in the validation of natural products for the treatment of obesity mediated by gut microbiota.Therefore,fecal microbiota transplantation is expected to be a promising approach for the treatment of obesity and the study of natural products-mediated weight loss activity of gut microbes.Chitosan oligosaccharide(COS)is the only cationic basic oligosaccharide with various biological activities.The previous experiments of our group showed that COSM(MW ≤ 3000 Da)has good weight loss activity,which can reverse the intestinal microbes in obese mice and reduce the Firmicutes/Bacteroidetes ratio.Therefore,this project took the gut microbes after COSM intervention as the research object,and took the pseudoaseptic mice induced by high fat and sugar diet as the model.The intestinal fecal bacterial fluid after COSM intervention was administered by gavage to explore the transfer effect of the lipid-lowering activity of COSM in the treatment of obesity.To further explore the energy metabolism mechanism of pseudoaseptic mice under high fat and sugar diet environment after fecal microbiota transplantation.After 4 weeks of mixed antibiotic drinking water intervention in a high fat and sugar diet environment,the diversity and abundance of intestinal microbes in mice were significantly reduced,proving that this method can successfully establish pseudoaseptic mice model in the high fat and sugar diet environment.The results of fecal microbiota transplantation showed that the gut microbes after COSM intervention had better weight loss and lipid-lowering activities.It relieves weight gain and body fat rate induced by high-fat and high-sugar diet,inhibits excessive growth of adipocytes,promotes energy metabolism,and regulates the levels of four blood lipids:TG,TC,LDL-C and HDL-C and lipid metabolites NEFA and TBA,improve glucose tolerance.The intestinal barrier function test found that the gut microbes after COSM intervention promoted the expression of the intestinal tight junction protein Occludin to a certain extent.Analysis of 16 S r RNA results showed that the gut microbes after COSM intervention down-regulated the ratio of Firmicutes/Bacteroidetes induced by high-fat and sugar to a certain extent,up-regulated the gut microbial diversity and the abundance of bacteria associated with bile acid metabolism,and promoted the abundance of bacteria associated with body thermogenesis and anti-obesity.Further bile acid profiling analysis found that free bile acids CA,LCA,β-MCA and α-MCA were significantly up-regulated by gut microbes after COSM intervention.Through Spearman correlation analysis,it was found that Clostridium,Ruminococcus,Bacteroides and Streptococcus bacteria that promote bile acid metabolism were positively correlated with bile acids CA,LCA,DCA and CDCA,while thermogenesis-related flora Adlercreutzia,Akkermansia and CA,β-MCA,α-MCA and LCA were positively correlated.Mechanistic studies have shown that gut microbes after COSM intervention can promote the natural ligands LCA and CA of TGR5 receptor by regulating bile acid metabolism and thermogenesis-related gut microbes in the body,and activate the TGR5-Dio2-UCP1 pathway.and further regulate thermogenesis factors of brown adipose tissue PGC-1α,PRDM16 and PPARγ and fatty acid oxidation factors of brown adipose tissue PPARα,CPT1α,CPT1 b and MCAD.In summary,based on the intestinal microbes as the research object,the effect and mechanism of the weight loss activity of the intestinal microbes after COSM intervention were explored through a pseudoaseptic mouse model under a high-fat and high-sugar diet environment.The experimental results demonstrate that COSM can exert anti-obesity activity by improving the abundance of obesity-related gut microbes,while regulating the thermogenesis factor and fatty acid oxidizing factor in brown fat,and promoting the body’s energy metabolism. |
