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微生物组及其药理学潜力。

The Microbiome and Its Potential for Pharmacology.

作者信息

Chavira Aries, Belda-Ferre Pedro, Kosciolek Tomasz, Ali Farhana, Dorrestein Pieter C, Knight Rob

机构信息

Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA.

Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.

出版信息

Handb Exp Pharmacol. 2019;260:301-326. doi: 10.1007/164_2019_317.

Abstract

The human microbiota (the microscopic organisms that inhabit us) and microbiome (their genes) hold considerable potential for improving pharmacological practice. Recent advances in multi-"omics" techniques have dramatically improved our understanding of the constituents of the microbiome and their functions. The implications of this research for human health, including microbiome links to obesity, drug metabolism, neurological diseases, cancer, and many other health conditions, have sparked considerable interest in exploiting the microbiome for targeted therapeutics. Links between microbial pathways and disease states further highlight a rich potential for companion diagnostics and precision medicine approaches. For example, the success of fecal microbiota transplantation to treat Clostridium difficile infection has already started to redefine standard of care with a microbiome-directed therapy. In this review we briefly discuss the nature of human microbial ecosystems and with pathologies and biological processes linked to the microbiome. We then review emerging computational metagenomic, metabolomic, and wet lab techniques researchers are using today to learn about the roles host-microbial interactions have with respect to pharmacological purposes and vice versa. Finally, we describe how drugs affect the microbiome, how the microbiome can impact drug response in different people, and the potential of the microbiome itself as a source of new therapeutics.

摘要

人类微生物群(寄居于我们体内的微生物)和微生物组(它们的基因)在改善药理学实践方面具有巨大潜力。多“组学”技术的最新进展极大地增进了我们对微生物组组成及其功能的理解。这项研究对人类健康的影响,包括微生物组与肥胖、药物代谢、神经疾病、癌症以及许多其他健康状况的关联,引发了人们对利用微生物组进行靶向治疗的浓厚兴趣。微生物途径与疾病状态之间的联系进一步凸显了伴随诊断和精准医学方法的巨大潜力。例如,粪便微生物群移植治疗艰难梭菌感染的成功已经开始用微生物组导向疗法重新定义治疗标准。在这篇综述中,我们简要讨论人类微生物生态系统的性质以及与微生物组相关的病理学和生物学过程。然后,我们回顾研究人员目前正在使用的新兴计算宏基因组学、代谢组学和湿实验室技术,以了解宿主 - 微生物相互作用在药理学方面的作用,反之亦然。最后,我们描述药物如何影响微生物组,微生物组如何影响不同人群的药物反应,以及微生物组本身作为新治疗方法来源的潜力。

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