摘要
Objective:This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules(QFG)in inhibiting colitis-associated colorectal cancer(CAC)development via RNA sequencing(RNA-seq)and16S ribosomal RNA(rRNA)correlation analysis.Methods:CAC was induced in BALB/c mice using azoxymethane(AOM)and dextran sulfate sodium(DSS),and QFG was administered orally to the treatment group.The effects of QFG on CAC were evaluated using disease index,histology,and serum T-cell ratios.RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change.Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence.The link between microbiota and CACrelated markers was explored using linear discriminant analysis effect size and Spearman correlation analysis.Results:Long-term treatment with QFG prevented AOM/DSS-induced CAC formation,reduced levels of interleukin(IL)-1βtumor necrosis factor-alpha(TNF-α),IL-6,and interferon y(IFN-y),and increased CD3^(+)and CD4^(+)/CD8^(+)T cells ratio,without causing hepatic or renal toxicity.A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances.Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2(NOD2)/nuclear factor kappa-B(NF-κB)pathway as key for QFG's treatment against CAC.Furthermore,QFG decreased the abundance of Bacilli,Bacillales,Staphylococcaceae,Staphylococcus,Lactobacillales,Aerococcus,Alloprevotella,and Akkermansia,while increasing Clostridiales,Lachnospiraceae,LachnospiraceaeNK4A136group,Ruminococcaceae,and Muribaculaceae,which were highly correlated with CAC-related markers or NOD2/NF-kB pathway.Conclusion:By mapping the relationships between CAC,immune responses,microbiota,and key pathways,this study clarifies the mechanism of QFG in inhibiting CAC,highlighting its potential for clinical use as preventive therapy.
基金
supported by the National Natural Science Foundation of China(No.82204925)
the Financial Project of Fujian Province(No.X2024004)
the Natural Science Foundation of Fujian Province,China(No.2024J01782,2022J01368)。
作者简介
co-first author:Bin Huang;co-first author:Honglin An;Corresponding author:Ruiguo Wang,E-mail address:312043068@qq.com;Corresponding author:Jiumao Lin,E-mail address:linjiumao@fjtcm.edu.cn。
