Non-absorbable antibiotic treatment inhibits colorectal cancer liver metastasis by modulating deoxycholic acid metabolism by intestinal microbes

Deng, Junjie; Yuan, Wei; Tan, Qin; Wei, Xundong; Ma, Jie

doi:10.7150/jca.63490

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J Cancer 2022; 13(3):764-774. doi:10.7150/jca.63490 This issue Cite

Research Paper

Non-absorbable antibiotic treatment inhibits colorectal cancer liver metastasis by modulating deoxycholic acid metabolism by intestinal microbes

Junjie Deng^1,2, Wei Yuan¹, Qin Tan², Xundong Wei^2✉, Jie Ma^2✉

1. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P.R. China.
2. Center of Biotherapy, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, P.R. China.

✉ Corresponding authors: Xundong Wei, Center of Biotherapy, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Dongdan Dahua Road, Beijing 10 More

Citation:

Deng J, Yuan W, Tan Q, Wei X, Ma J. Non-absorbable antibiotic treatment inhibits colorectal cancer liver metastasis by modulating deoxycholic acid metabolism by intestinal microbes. J Cancer 2022; 13(3):764-774. doi:10.7150/jca.63490. https://www.jcancer.org/v13p0764.htm

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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 7α-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.

Keywords: Microbes, Colorectal cancer, Tumor metastasis, Deoxycholic acid

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APA

Deng, J., Yuan, W., Tan, Q., Wei, X., Ma, J. (2022). Non-absorbable antibiotic treatment inhibits colorectal cancer liver metastasis by modulating deoxycholic acid metabolism by intestinal microbes. Journal of Cancer, 13(3), 764-774. https://doi.org/10.7150/jca.63490.

ACS

Deng, J.; Yuan, W.; Tan, Q.; Wei, X.; Ma, J. Non-absorbable antibiotic treatment inhibits colorectal cancer liver metastasis by modulating deoxycholic acid metabolism by intestinal microbes. J. Cancer 2022, 13 (3), 764-774. DOI: 10.7150/jca.63490.

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CSE

Deng J, Yuan W, Tan Q, Wei X, Ma J. 2022. Non-absorbable antibiotic treatment inhibits colorectal cancer liver metastasis by modulating deoxycholic acid metabolism by intestinal microbes. J Cancer. 13(3):764-774.

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