Non-absorbable antibiotic treatment inhibits colorectal cancer liver metastasis by modulating deoxycholic acid metabolism by intestinal microbes
Junjie Deng, Wei Yuan, Qin Tan, Xundong Wei, Jie Ma
Abstract
Emerging evidence suggests that intestinal microbes influence the occurrence and development of colorectal cancer (CRC). However, few studies have examined the relationship between gut bacteria and liver metastasis of CRC. In this study, we found that administration of non-absorbable antibiotics inhibited liver metastasis of CRC in a mouse model compared with a control group. To elucidate the underlying mechanism, immune cell infiltration analysis, 16S rRNA sequencing, and metabolomics were performed. Differential analysis revealed that non-absorbable antibiotic treatment significantly altered gut microbial diversity and decreased the concentration of deoxycholic acid (DCA) in feces and liver tissues. Furthermore, we verified that bacteria capable of converting cholic acid (CA) to DCA via 7-dehydroxylation were reduced in mice treated with non-absorbable antibiotics. Finally, in vitro and in vivo experiments confirmed that DCA accelerated the proliferation and metastasis of CRC cells.