近日，德国欧洲分子生物学实验室Michael Zimmermann等研究人员合作发现，肠道微生物群致癌物代谢导致远端组织肿瘤。2024年7月31日，《自然》杂志在线发表了这项成果。

研究人员展示了肠道微生物群的耗竭影响亚硝胺的毒代动力学，这显著减少了小鼠亚硝胺诱导的膀胱癌的发展和严重性。研究人员通过体外和体内使用个性化的细菌培养集合和无菌小鼠模型，将这种致癌物生物转化与特定的肠道细菌分离株因果联系起来。

研究人员测试了来自不同人类供体的肠道群落，以证明微生物致癌物代谢在个体之间存在差异，并且研究人员展示了这种代谢活性适用于结构相关的亚硝胺致癌物。总之，这些结果表明，肠道微生物群致癌物代谢可能是化学诱导的致癌作用的一个促成因素，这可能为靶向微生物群以改善易感风险评估和癌症预防开辟途径。

研究人员表示，暴露于环境污染物和人体微生物群组成是肿瘤发展的重要易感因素。与药物分子类似，污染物通常在体内代谢，这可以改变它们的致癌潜力并通过改变毒代动力学影响组织分布。尽管最近的研究表明，人类相关的微生物可以化学转化广泛的外源物并影响生成代谢物的特征和组织暴露，但微生物生物转化对化学诱导的肿瘤发展的影响仍不清楚。

附：英文原文

Title: Gut microbiota carcinogen metabolism causes distal tissue tumours

Author: Roje, Blanka, Zhang, Boyao, Mastrorilli, Eleonora, Kovai, Ana, Suak, Lana, Ljubenkov, Ivica, osi, Elena, Vilovi, Katarina, Metrovi, Antonio, Vukovac, Emilija Lozo, Buevi-Popovi, Viljemka, Puljiz, eljko, Karaman, Ivana, Terzi, Jano, Zimmermann, Michael

Issue&Volume: 2024-07-31

Abstract: Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development1,2. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics3. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites4,5, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice6,7. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer.

DOI: 10.1038/s41586-024-07754-w

Source: https://www.nature.com/articles/s41586-024-07754-w