在癌症治疗过程中细菌操作子的扩张改善了胺的毒性
Kai R Trepka1, Wesley A Kidder2,3, Than S Kyaw1
1Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Science translational medicine
|April 16, 2025
概括
肠道细菌的preTA操作子使化疗药物5-甲 (5-FU) 失活,降低了其毒性. 这一发现为癌症患者的化疗副作用管理提供了新的策略.
科学领域:
- 微生物组研究的研究.
- 癌症治疗治疗 癌症治疗
- 药理学 药理学是指药理学的学科.
背景情况:
- 药物毒性限制了癌症治疗的有效性和发展.
- 人类遗传学很难预测药物的副作用.
- 人们越来越认识到肠道微生物在药物代谢中的作用.
研究的目的:
- 为了研究肠道微生物对结直肠癌治疗期间的胺毒性的影响.
- 确定有助于药物无活化和毒性调节的特定微生物因素.
主要方法:
- 在结直肠癌治疗期间,人类肠道微生物组的纵向16S rRNA和元基因组测序.
- 使用细胞培养,无细菌小鼠和用抗生素治疗的小鼠进行了ex vivo和in vivo实验.
- 在5-甲 (5-FU) 失活中,preTA操作子在5-甲 (5-FU) 失活中的作用的功能分析.
主要成果:
- 口服胺治疗导致肠道微生物社区结构和胺相关基因丰度发生显著变化.
- 预TA操作子得到了丰富,并证明了在体外,体外和体内无效化5-FU的能力.
- 没有细菌和接受抗生素治疗的小鼠表现出增加的胺毒性,微生物群或TA+前细菌殖民改善了这种毒性.
- 在患者中,较高的preTA丰度与降低的胺毒性相关.
结论:
- 在肠道细菌前TA操作子和胺剂量限制毒性之间存在直接的,临床相关的联系.
- 针对preTA操作子提供了一种潜在的策略,以减轻化疗诱导的副作用.
- 这种宿主微生物群相互作用框架可以应用于其他药物,包括癌症免疫疗法.
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