基于微生物组和代谢组学探讨益气健运方改善小鼠肥胖病的作用机制OA

Objective To investigate the efficacy and mechanisms of Yiqi Jianyun Formula(益气健运方,YQJYF)in an obese mouse model by integrating microbiome and metabolomic analyses.Methods Forty male C57BL/6 mice were randomly assigned to five groups(n=8 per group):control(CON,standard diet),high-fat diet(HFD),positive control(orlistat,ORL),low-dose YQJYF(YQL),and high-dose YQJYF(YQH).Mice received daily gavage for 12 weeks.After intervention,we evaluated serum biochemical parameters,histopathology of liver and epididymal white adipose tissue(eWAT),gut microbiota(GM)profiling via 16S rRNA sequencing,and metabolic profiling via untargeted metabolomics.Results Compared to CON,HFD mice showed significant increase in body weight,adi‑posity,serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),glucose(GLU),fasting insulin(FINS),inflammatory markers(IL-1β,TNF-α,IL-6),lipopolysaccharide(LPS),liver enzymes(AST,ALT),hepatic lipid accumu‑lation,hepatocyte swelling,and eWAT adipocyte hypertrophy(P<0.01).Interventions with ORL,YQL,and YQH significantly attenu‑ated these HFD-induced alterations,lowering body weight,adiposity,serum lipid/glucose/insulin levels,and liver enzyme activities(P<0.05 or P<0.01).Notably,YQL and YQH markedly reduced serum IL-1β,TNF-α,IL-6,and LPS(P<0.05 or P<0.01)and improved hepatic and eWAT histology.YQJYF modulated GM by decreasing the Firmicutes/Bacteroidetes ratio,suppressing genera such as Turicibacter,Romboutsia,Eubacterium fissicatena,and Enterorhabdus,while promoting Roseburia,Oscillospiraceae,and Colidextrib-acter.Metabolomics revealed that YQJYF suppressed levels of phosphatidylcholines(PCs),lysophosphatidylcholines(LysoPCs),pros‑taglandin E2,and arachidonic acid,while elevating linoleic acid,phytosphingosine,and stercobilin.Pathway analysis indicated modu‑lation of linoleic acid,α-linolenic acid,glycerophospholipid,and arachidonic acid metabolism.Conclusion YQJYF ameliorates obe‑sity,improves glucose-lipid metabolism,reduces systemic inflammation,and alleviates hepatic and adipose tissue pathology in HFD-fed mice,likely through restoring gut microbial balance and regulating key lipid-inflammatory metabolic pathways.