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YH说 许多药物或治疗方案对于不同的患者来说疗效有差异，这种差异对患者的治疗有一定的影响。造成这种差异的原因尚未明确。本文通过检测76种人体肠道细菌代谢271种口服药物的能力，发现这种差异可能与肠道微生物代谢有关。肠道微生物群可能会产生代谢药物的酶，对药物的激活灭活等产生影响。此研究结果有利于开拓利用个体微生物的方法治疗的新思路。 Mapping human microbiome drug metabolism by gut bacteria andtheir genes 图片来源：文献原文 Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing evidence implicates the gut microbiome in this variability, the molecular mechanisms involved remain largely unknown. Here we show, by measuring the ability of 76 human gut bacteria from diverse clades to metabolize 271 orally administered drugs, that many drugs are chemically modified by microorganisms. We combined high-throughput genetic analyses with mass spectrometry to systematically identify microbial gene products that metabolize drugs. These microbiome-encoded enzymes can directly and substantially affect intestinal and systemic drug metabolism in mice, and can explain the drug-metabolizing activities of human gut bacteria and communities on the basis of their genomic contents. These causal links between the gene content and metabolic activities of the microbiota connect interpersonal variability in microbiomes to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications. 通过肠道细菌及其基因定位人类微生物组药物代谢 个体对药物的反应差异很大，而且存在治疗延迟和不良反应，这些药物可能存在危险性并且价格昂贵。虽然越来越多的证据表明肠道微生物群存在变异，但所涉及的分子机制仍不清楚。在此，我们通过检测76种人体肠道细菌代谢271种口服药物的能力，发现许多药物都是由微生物进行化学修饰的。我们通过高通量遗传分析与质谱结合，系统鉴定代谢药物的微生物群基因产物。这些微生物群编码的酶可以直接影响小鼠的肠道和全身药物代谢，并根据其基因组含量解释人类肠道细菌的药物代谢活性。这些微生物群的的基因含量和代谢活性之间的关系将微生物组中的个体差异与药物代谢中的个体差异联系起来，这对多种疾病适应症的药物治疗和药物开发都有意义。 文献来源 Nature|doi:10.1038/s41586-019-1291-3 备注：浦美医学每周推出一个专题的“文献速递”汇编，如需详细了解内容或全文请联系我们（浦美小编：微信号pumeixiaobian）。文献内容均由浦美医学编译自原文，疏漏之处敬请读者指正。 |
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