Cell：鉴定不同个体肠道菌群药物代谢作用的新方案
- ①基于单一粪便样本的研究，初步建立了可被菌群代谢的药物（MCM）的筛选方法，并通过该方法鉴定获得45种新MCM药；
- ②采用更严格的方法确定最佳培养基、定量药物和代谢物以及鉴定未知代谢物，优化实验方案；
- ③使用新方案对20名捐赠者的样本和23种药物进行分析，发现肠道菌群代谢药物存在个体差异；
- ④结合宏基因组功能信息，鉴定获得了参与药物代谢的具体微生物衍生酶，证明了该方法的生化潜力；
- ⑤在小鼠中验证了菌群对卡培他滨的去糖基化作用。
主编推荐语
药物微生物组是菌群研究的新兴热点之一。近期的许多研究表明，肠道菌群的差异或可解释部分药物在个体间的药效差异。然而由于微生物组的复杂性，以及在多种条件下测试数百种药物和数千种代谢产物的巨大技术挑战，导致目前缺乏关于肠道菌群代谢药物的系统性研究。而该研究所提出的MCM-Screen定量实验方案，为药物微生物组的研究提供了新手段，或将进一步推动药物微生物组的发展。有兴趣的读者不妨搭配着阅读之前发表的另一篇关于肠道菌群药物代谢作用的系统性研究（
查看文章）。
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延伸阅读本研究的原文信息和链接出处，以及相关解读和评论文章。欢迎读者朋友们推荐！
Personalized Mapping of Drug Metabolism by the Human Gut Microbiome
肠道菌群代谢药物的个性化图谱
10.1016/j.cell.2020.05.001
2020-06-10, Article
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The human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities. Dozens of drugs have been shown to be metabolized by single isolates from the gut microbiome, but the extent of this phenomenon is rarely explored in the context of microbial communities. Here, we develop a quantitative experimental framework for mapping the ability of the human gut microbiome to metabolize small molecule drugs: Microbiome-Derived Metabolism (MDM)-Screen. Included are a batch culturing sys- tem for sustained growth of subject-specific gut microbial communities, an ex vivo drug metabolism screen, and targeted and untargeted functional metagenomic screens to identify microbiome-encoded genes responsible for specific metabolic events. Our framework identifies novel drug-microbiome interactions that vary between individuals and demonstrates how the gut microbiome might be used in drug development and personalized medicine.
First Authors:
Bahar Javdan
Correspondence Authors:
Mohamed S Donia
All Authors:
Bahar Javdan,Jaime G Lopez,Pranatchareeya Chankhamjon,Ying-Chiang J Lee,Raphaella Hull,Qihao Wu,Xiaojuan Wang,Seema Chatterjee,Mohamed S Donia
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