Tutorial: Microbiome studies in drug metabolism.

Tutorial: Microbiome studies in drug metabolism.
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DOI:
10.1111/cts.13416
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发表时间:
2022-12
影响因子:
3.9
通讯作者:
Cann, Isaac
Cann, Isaac
中科院分区:
医学3区
文献类型:
--
作者:
Dodd, Dylan;Cann, Isaac

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人类胃肠道是大量微生物的家园,这些微生物的新陈代谢影响着人类的健康和生理机能。肠道微生物组编码数百万个基因,其产物赋予我们的身体独特的生化活性。在药物代谢的背景下,肠道微生物生物化学通过两种主要方式影响人类:(1)通过产生调节人类 I 和 II 相途径表达和活性的小分子; (2)直接修改给予人类的药物以产生活性、非活性或有毒的代谢物。尽管微生物组调节药物代谢的能力早已为人所知,但最近的研究在更广泛的范围内探索了这些相互作用,并揭示了前所未有的微生物药物代谢范围。这项工作的意义在于,我们或许能够预测个体微生物组代谢药物的能力,并利用这些信息来避免毒性并告知正确的剂量。在这里,我们提供了如何在药物代谢背景下研究微生物组的教程,重点关注体外、啮齿动物和人类研究。然后我们强调该领域的一些局限性和机遇。
The human gastrointestinal tract is home to a dense population of microorganisms whose metabolism impacts human health and physiology. The gut microbiome encodes millions of genes, the products of which endow our bodies with unique biochemical activities. In the context of drug metabolism, microbial biochemistry in the gut influences humans in two major ways: (1) by producing small molecules that modulate expression and activity of human phase I and II pathways; and (2) by directly modifying drugs administered to humans to yield active, inactive, or toxic metabolites. Although the capacity of the microbiome to modulate drug metabolism has long been known, recent studies have explored these interactions on a much broader scale and have revealed an unprecedented scope of microbial drug metabolism. The implication of this work is that we might be able to predict the capacity of an individual's microbiome to metabolize drugs and use this information to avoid toxicity and inform proper dosing. Here, we provide a tutorial of how to study the microbiome in the context of drug metabolism, focusing on in vitro, rodent, and human studies. We then highlight some limitations and opportunities for the field.
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