基于"肠菌-胆汁酸"代谢探讨补中益气汤改善5-FU诱导的化疗肌少症大鼠模型的作用机制OA

Objective To investigate whether Buzhong Yiqi Decoction(BZYQD)ameliorates 5-fluorouracil(5-FU)-induced chemotherapy-induced sarcopenia(CIS)by regulating the"gut microbiota-bile acid metabolism"axis.Methods SPF-grade male SD rats were randomly divided into control(C),model(M),low-dose BZYQD(LBYD),and high-dose BZYQD(HBYD)groups(n=7 per group).Except for C group,all other groups were modeled by intraperitoneal injection of 28 mg/(kg·d)5-FU for 6 consecutive days to establish the CIS model.Starting from the first day of modeling,the BZYQD groups were gavaged with BZYQD,while the C and M groups received an equal volume of 0.9％sodium chloride solution once daily for 15 d.The general condition of the rats was recorded.Gastrocnemius muscle pathological changes were assessed by hematoxylin and eosin staining,and the cecal microbiota structure was analyzed using 16S rDNA sequencing.Cecal bile acid levels were determined using ultra-high performance liquid chromatography-tandem mass spectrometry,and corr-elation analysis between microbiota and bile acids was performed.Results Compared with the C group,the M group showed significant reductions in body mass,gastrocnemius relative to wet mass,grip strength,gastrocnemius muscle fiber cross-sectional area,and exhaustive swimming time(23.69％,34.41％,28.39％,34.66％,and 50.48％,respectively).These changes were accompanied by decreased gut microbiota diversity,reduced abundance of probiotics(Lactobacillus and Bifidobacterium),and increased abundance of the pathogenic bacterium Desulfovibrio.Disordered bile acid metabolism was observed,including lithocholic acid(LCA)and deoxycholic acid,while the level of the Farnesoid X receptor(FXR)antagonist tauro-β-muricholic acid(T-β-MCA)was significantly increased.Compared with the M group,BZYQD intervention,particularly at the high dose,significantly restored muscle fiber cross-sectional area,improved grip strength,and prolonged exhaustive swimming time.Additionally,it increased the abundance of Lactobacillus,decreased that of Desulfovibrio,elevated LCA content,and reduced the T-β-MCA/taurocholic acid(TCA)ratio.Correlation analysis revealed significant associations among Lactobacillus,Bifidobacterium,Ruminococcaceae,Desulfovibrio and bile acids,including LCA and chenodeoxycholic acid.Conclusions Buzhong Yiqi decoction may ameliorate 5-FU-induced CIS by remodeling the gut microbiota,correcting bile acid metabolic disorders,and subsequently modulating related signaling pathways.