Objective To investigate the mechanism of Wumei Pill (乌梅丸) in delaying the transformation of colitis cancer using microbiome and metabolomics. Methods A colitis cancer transformation animal model was constructed using azoxymethane (AOM)/dextran sulfate sodium (DSS). A total of 32 C57BL/6J mice were randomly divided into control group, model group, and Wumei Pill low-, high-dose (11.18, 22.36 g/kg) groups. Colonic tumor progression and histopathological changes were evaluated by intestinal endoscopic observation, macroscopic specimen assessment and hematoxylin-eosin (HE) staining. Levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in serum, and levels of total bile acids (TBA), cholic acid (CA), deoxycholic acid (DCA), lithocholic acid (LCA) in serum and in feces were measured by ELISA. 16S rRNA sequencing technology was used to analyze gut microbial diversity and species abundance. The abundance of metabolites was assessed by non-targeted metabolomics analysis. qRT-PCR was used to verify the expression changes of Clostridium scindens (C. scindens), Clostridium hylemonae (C. hylemonae), Clostridium hiranonis (C. hiranonis) and the coenzyme A transferase encoding gene BaiF. Results Compared with model group, the intervention of Wumei Pill could delay the transformation of colitis cancer, and the therapeutic effect was better at low dose of Wumei Pill. Low dose Wumei Pill could significantly reduce the number of colon tumors (P < 0.001), lower colitis and tumor pathology scores (P < 0.05, 0.01), and lower levels of IL-6 and TNF-α in serum (P < 0.01, 0.001). The microbiological results showed that Wumei Pill could improve the structure of intestinal microbiota, reduce the abundance of opportunistic pathogenic bacteria such as Clostridium, and increase the abundance of probiotics such as Lactobacillus and Roseburia. The non-targeted metabolomics results showed that there were 82 differential metabolites between Wumei Pill low-dose group and model group, significantly enriched in secondary bile acid metabolism pathway. Wumei Pill could significantly reduce the levels of TBA, CA,and DCA in serum and feces (P < 0.05, 0.01, 0.001). qRT PCR results further confirmed that Wumei Pill could inhibit bacteria involved in DCA synthesis such as C. scindens and C. hylmonae (P < 0.05), and lead to a decrease in BaiF gene expression level (P < 0.001). Conclusion Wumei Pill could alleviate colitis and delay the progression of inflammatory cancer by modulating the bile acid homeostasis mediated by gut microbiota, reducing the abundance and dehydroxylation function of bacteria such as C. scindens, and decreasing the production of DCA.

colitis cancer  /  Wumei Pill  /  bile acid  /  gut microbiota  /  Clostridium scindens  /  Clostridium hylemonae  /  phellodendrine chloride  /  coptisine hydrochloride  /  berberine hydrochloride