大柴胡汤对2型糖尿病小鼠的疗效及肠道菌群调节作用OA

Objective:To investigate the therapeutic efficacy of Dachaihu Decoction in a mouse model of type 2 diabetes mellitus(T2DM)and its regulatory effects on the gut microbiota using 16S rRNA sequencing.Methods:The T2DM model was established in thirty 6-week-old male C57BL/6J mice by inducing them with a high-fat diet and intraperito-neal injections of streptozotocin(STZ).Post-modeling,the mice were randomly allocated into a model group,a Dachaihu decoction group,and a metformin group,with 10 mice per group.A normal control group consisting of age-matched male C57BL/6J mice was also included.The Dachaihu Decoction and metformin groups received their respec-tive treatments via daily gavage for 8 weeks,while the normal and model groups received an equivalent volume of nor-mal saline.Body weight and fasting blood glucose(FBG)were monitored throughout the treatment period.At the end of the 8 weeks,an oral glucose tolerance test(OGTT)and an insulin tolerance test(ITT)were conducted,after which the mice were anesthetized for sample collection.Liver function and serum lipid profiles were analyzed using an auto-mated biochemical analyzer.Histopathological changes and lipid accumulation in the liver were assessed through He-matoxylin and Eosin(H&E)and Oil Red O staining.Alterations in the gut microbial community and structure were e-valuated using 16S rRNA sequencing.Results:Compared to the model group,treatment with Dachaihu Decoction led to a significant reduction in body weight and FBG levels(P<0.01)and a marked improvement in glucose tolerance and insulin resistance(P<0.01).Dachaihu decoction also effectively ameliorated dyslipidemia,sig-nificantly lowering serum total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)(P<0.01),while increasing high-density lipoprotein cholesterol(HDL-C)(P<0.01).Further-more,Dachaihu decoction decreased the activity of alanine aminotransferase(ALT)and aspartate aminotrans-ferase(AST)(P<0.01).H&E and Oil Red O staining results showed that Dachaihu decoction significantly improved liver pathological changes and lipid deposition.16S rRNA sequencing revealed that Dachaihu Decoc-tion administration significantly increased the α-diversity of the gut microbiota and reversed the overall micro-bial dysbiosis observed in the model group.At the phylum level,Dachaihu Decoction decreased the Firmi-cutes/Bacteroidota ratio.Linear discriminant analysis Effect Size(LEfSe)identified a significant enrichment of Bacteroidota as a signature phylum in the Dachaihu decoction group.PICRUSt2 functional prediction indi-cated that Dachaihu Decoction downregulated hyperactivated carbohydrate metabolism and membrane trans-port pathways,while upregulating suppressed pathways related to amino acid metabolism,glycan biosynthesis and metabolism,and energy metabolism.Correlation analysis confirmed a strong association between the mi-crobial shifts induced by Dachaihu Decoction and the improved metabolic phenotypes.Conclusion:Dachaihu Decoction effectively ameliorates metabolic disorders,insulin resistance,and hepatic steatosis in T2DM mice.The underlying mechanism is likely closely associated with the modulation of gut microbiota composition,res-toration of its ecological balance,and normalization of its functional pathways.