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

TL;DR

This study shows that (E)-Flavokawain A helps prevent colorectal cancer in mice by changing gut bacteria and reducing inflammation.

Contribution

The study reveals FKA's novel protective mechanism against CRC through microbiota modulation and metabolic pathway regulation.

Findings

FKA inhibited colorectal cancer progression in mice by altering gut microbiota composition.

FKA suppressed pathogenic bacteria and boosted beneficial bacteria, reducing endotoxin levels.

FKA regulated lipid and arachidonic acid metabolism to mitigate inflammation in CRC.

Abstract

(E)-Flavokawain A (FKA), the primary chalcone constituent of Piper methysticum, exhibits diverse pharmacological properties and holds significant potential for therapeutic development. Objectives: This study aims to investigate the anti-colorectal cancer effects and mechanisms of FKA. Methods: 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. Results: 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. Conclusions: These findings provide valuable insights supporting the potential of FKA as a viable preventive strategy against CRC.

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