Integrated 16S rRNA Sequencing and Metabolomics Analysis Reveal the Protective Effects of (E)-Flavokawain A on AOM/DSS-Induced Colorectal Cancer in Mice

(E)-Flavokawain A (FKA), the primary chalcone constituent of <i>Piper methysticum</i>, exhibits diverse pharmacological properties and holds significant potential for therapeutic development. <b>Objectives</b>: This study aims to investigate the anti-colorectal cancer effects and mechanisms of FKA. <b>Methods</b>: Using AOM/DSS-induced colorectal cancer models in C57 mice, the research examines the impact of different FKA doses, employing 16S rRNA and metabolomics to explore the potential mechanism. <b>Results</b>: The findings indicated that FKA significantly inhibited the progression of colorectal cancer in C57 mice by modulating the composition of the gut microbiota. This modulation involved the suppression of endotoxin secretion by pathogenic bacteria and the concurrent augmentation of beneficial bacteria. Furthermore, in the context of metabolic pathways, FKA regulates lipid metabolism and arachidonic acid metabolism, thereby mitigating the inflammatory transformation associated with colorectal cancer. <b>Conclusions</b>: These findings provide valuable insights supporting the potential of FKA as a viable preventive strategy against CRC.