Integrated gut microbiota and metabolome analysis reveals the mechanism of Xiaoai Jiedu recipe in ameliorating colorectal cancer

IntroductionXiaoai Jiedu recipe (XJR), a classical prescription of traditional Chinese medicine (TCM), has been clinically proven to be effective in ameliorating colorectal cancer (CRC). However, its exact mechanism of action is still elusive, limiting its clinical application and promotion to a certain extent. This study aims to evaluate the effect of XJR on CRC and further illustrate mechanism underlying its action. MethodsWe investigated the anti-tumor efficacy of XJR in vitro and vivo experiments. An integrated 16S rRNA gene sequencing and UPLC-MS based metabolomics approach were performed to explore possible mechanism of XJR anti-CRC on the gut microbiota and serum metabolic profiles. The correlation between altered gut microbiota and disturbed serum metabolites was investigated using Pearson's correlation analysis. ResultsXJR effectively displayed anti-CRC effect both in vitro and in vivo. The abundance of aggressive bacteria such as Bacteroidetes, Bacteroides, and Prevotellaceae decreased, while the levels of beneficial bacteria increased (Firmicutes, Roseburia, and Actinobacteria). Metabolomics analysis identified 12 potential metabolic pathways and 50 serum metabolites with different abundances possibly affected by XJR. Correlation analysis showed that the relative abundance of aggressive bacteria was positively correlated with the levels of Arachidonic acid, Adrenic acid, 15(S)-HpETE, DL-Arginine, and Lysopc 18:2, which was different from the beneficial bacteria. DiscussionThe regulation of gut microbiota and related metabolites may be potential breakthrough point to elucidate the mechanism of XJR in the treatment of the CRC. The strategy employed would provide theoretical basis for clinical application of TCM.