Deng Junjie, Yuan Wei, Tan Qin, Wei Xundong, Ma Jie
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.
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.
J Cancer. 2022 Jan 1;13(3):764-774. doi: 10.7150/jca.63490. eCollection 2022.
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, and experiments confirmed that DCA accelerated the proliferation and metastasis of CRC cells.
新出现的证据表明,肠道微生物会影响结直肠癌(CRC)的发生和发展。然而,很少有研究探讨肠道细菌与CRC肝转移之间的关系。在本研究中,我们发现与对照组相比,给予不可吸收抗生素可抑制小鼠模型中CRC的肝转移。为阐明潜在机制,我们进行了免疫细胞浸润分析、16S rRNA测序和代谢组学研究。差异分析显示,不可吸收抗生素治疗显著改变了肠道微生物多样性,并降低了粪便和肝组织中脱氧胆酸(DCA)的浓度。此外,我们证实,在用不可吸收抗生素治疗的小鼠中,能够通过7α-脱羟基作用将胆酸(CA)转化为DCA的细菌减少。最后,实验证实DCA加速了CRC细胞的增殖和转移。