摘要Objective:To explore whether polysaccharide of Danggui Buxue Decoction(formula polysaccharide,FP)could attenuate colorectal cancer(CRC)via modulating intestinal microflora and metabolites.Methods:A total of 30 male C57BL/6 mice were randomly assigned to 3 groups according to body weight,including normal control,CRC model and FP groups(n=10).Dextran sulfate sodium and azoxymethane were used to induce CRC model.The mice in FP group were treated with FP[0.9 g/(kg·d)]for 8 weeks.Then the coloretal length,weight and tumors number of colorectal tissues were observed.Colonic tissues were stained with hematoxylin and eosin to evaluate the histological changes.Tight junction proteins including claudin 1 and zonula occludens-1(ZO-1)were detected using immunohistochemistry.Serum concentrations of endothelial cell specific molecule-1 and carcino embryonic antigen were determined using enzyme-linked immunosorbent assays.Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)p65 signal-related mRNA and proteins expressions were detected using real-time polymerase chain reaction and Western blot,respectively.Feces samples were detected with 16S rRNA and liquid chromatography-mass spectrometry and non-targeted metabolomics sequencing was used to analyze the composition of intestinal microbiota and metabolic changes.Results:FP significantly inhibited colorectal tumor growth,attenuated body weight loss,repaired colonic structure,improved intestinal barrier dysfunction,reduced colonic inflammatory cytokine levels and inhibited TLR4/NF-κB pathway related mRNA and protein expressions(all P＜0.01).Moreover,FP altered the gut microbiota composition of CRC mice dramatically,characterized by a reduction of Firmicutes-Bacteroidetes ratio at the phylum level.FP suppressed Lachnospiraceae_NK4A136_group,Odoribacter and Romboutsia(P＜0.05 or P＜0.01),and elevated the abundance of Dubosiella,Candidatus_Saccharimonas and Alloprevotella at the genus level(P＜0.01).Non-targeted metabolomics sequencing detected significant differences in metabolites,and the functions of differential metabolites were focused on regulating amino acid metabolism,lipid metabolism and metabolism of cofactors and vitamins.Conclusions:FP attenuates colonic injury and intestinal inflammatory response in CRC mice,repairs disrupted-intestinal microbiota,and improves metabolites.This research provides experimental basis for application of FP as a potential therapeutic agent for CRC.