Study On The Mechanism Of Anti-Obesity Effect Of Ginseng Extract In High-Fat Induced Mice Model Using Metagene Sequencing Combined With Metabolomics

Objective: Use the fecal macro gene sequencing technology and serum non targeted metabonomic technology to systematically reveal the mechanism of ginseng extract in regulating the gut microbiota bacterial richness and metabolites,and inhibiting the weight gain of high-fat diet induced obese mice.Methods: The total protein,total polysaccharide and total saponin in ginseng extract were quantified by BCA protein quantification,phenol sulfuric acid method and Vanillin sulfuric acid method.Simultaneously administering ginseng extract and a high-fat diet in a weight dependent manner for 12 weeks to construct a DIO obesity mice model.Evaluate the weight loss effect of ginseng extract using Micro-CT,small animal body fat analysis system,blood biochemical testing,fat H&E staining,and liver oil red O staining methods.Use the fecal metagene sequencing technology to reveal the changes in the structure and diversity of gut microbiota in mice.Revealing changes in metabolic products in mice using serum non targeted metabolomics techniques.Identify the main metabolic pathways through correlation analysis,use the molecular biology methods to detect the expression of factors related to major metabolic pathways,comprehensively elucidate the efficacy and pharmacological mechanism of ginseng extract in significantly improving obesity in DIO mice.Results: The total protein content in ginseng extract is 3.51% ± 0.03%;The content of total saponins is 7.11% ± 0.18%;The content of total polysaccharides is 45.02% ± 1.04%.The results of weight gain and body fat analysis indicate that ginseng extract can reduce the weight growth rate of DIO mice by 15%,increase the proportion of lean meat,and reduce the proportion of fat meat.Micro CT and gross photos of the sample taken indicate that ginseng extract can significantly reduce fat volume,improve fat distribution,and inhibit lipid accumulation.The results of serum and liver biochemical analysis showed that ginseng extract significantly reduced total cholesterol and triglycerides in the liver,and improved liver damage.The macro gene sequencing results based on species level showed that there were2984 species of bacteria with differences between the Ctrl group and the HDF group,and 49 species with differences between the HFD group and the GE group,the strains with decreased relative abundance are mainly s＿Firmicutes bacteria M10-2,s＿Firmicutes bacteria ASF500,while the strains with increased relative abundance are mainly s＿Lachnospiraceae bacteria A4,s＿Eubacterium plexicaudatum.4845 metabolites were found in serum metabolomics,787 of which were different between HFD group and GE group,mainly including bile acids,amino acids,pyrimidines and other metabolites.Correlation analysis between macrogenes and metabolomics revealed s＿Firmicutes bacteria M10-2,s＿Eubacterium plexicaudatum has a significant correlation with bile acid metabolites.It is inferred that ginseng extract plays an anti-obesity role by regulating gut microbiota and then affecting Bile acid metabolism.Detected by PCR that ginseng extract can upregulate gene expression level of key factors of bile acid metabolism such as FXR,CYP8B1,CYP7B1,LXR-α.Conclusion: Ginseng extract may modulate the relative abundance of gut microbiota,such as s＿Firmicutes bacterium M10-2 and s＿Eubacterium plexicaudatum,promoted bile acid synthesis and transport,improved lipid metabolism,inhibited lipid accumulation in DIO mice,and exerted anti-obesity efficacy.