微生物维生素生物合成将肠道微生物群的动态与化疗毒性联系起来
Lars E Hillege1,2, Kai R Trepka3, Benjamin G H Guthrie3
1GROW-Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, Limburg, the Netherlands.
mBio
|May 20, 2025
概括
癌症药物的副作用可以通过产生维生素K2的肠道细菌来减少. 这项研究发现,随着capecitabine治疗,维生素K2生物合成基因增加,防止毒性并降低结直肠癌患者的神经病变.
科学领域:
- 微生物组研究的研究.
- 癌症治疗治疗 癌症治疗
- 毒性药物毒性 毒性药物毒性
背景情况:
- 剂量限制性毒性是癌症治疗的一个主要障碍.
- 人们越来越认识到肠道微生物群对抗癌药物疗效和毒性的作用,但患者数据有限.
- 了解capecitabine-microbiome相互作用对于管理治疗副作用至关重要.
研究的目的:
- 调查卡佩奇他 (CAP) 与晚期结直肠癌患者的肠道微生物组之间的相互作用.
- 确定有助于CAP引起的毒性微生物机制.
- 探索微生物代谢物的潜力,作为预测药物副作用的生物标志物.
主要方法:
- 从56名接受capecitabine治疗的晚期结直肠癌患者的便样本的纵向元基因组测序.
- 转子子子库屏幕,向基因删除和介质补充,以评估menaquinol生物合成在细菌耐药性中的作用.
- 对menaquinol基因和代谢物水平与外围感官神经病变的关联分析.
- 机器学习模型开发用于在独立队列中验证的毒性预测.
主要成果:
- 开普西他治疗显著改变了肠道微生物组合,丰富了menaquinol (维生素K2) 生物合成基因.
- 发现menaquinol生物合成可以保护*Escherichia coli*免受capecitabine毒性的影响.
- 便中menaquinol水平的增加与患者的外周感官神经病变减少有关.
- 机器学习模型在独立的患者队列中成功预测了毒性.
结论:
- 与治疗相关的微生物维生素生物合成增加,特别是menaquinol,对细菌和宿主细胞都起着化学保护作用.
- 微生物维生素生产是减轻癌症治疗副作用的潜在治疗目标.
- 这些发现为进一步的机制研究和改善癌症治疗结果的临床干预提供了基础.
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