Li Houkai, He Jiaojiao, Jia Wei
a Center for Chinese Medical Therapy and Systems Biology , Shanghai University of Traditional Chinese Medicine , Shanghai 201203 , China.
b Cancer Epidemiology Program , University of Hawaii Cancer Center , Honolulu , HI 96813 , USA.
Expert Opin Drug Metab Toxicol. 2016;12(1):31-40. doi: 10.1517/17425255.2016.1121234. Epub 2015 Dec 10.
Gut microbiota plays critical roles in drug metabolism. The variation of gut microbiota contributes to the interindividual differences toward drug therapy including drug-induced toxicity and efficacy. Accordingly, the investigation and elucidation of gut microbial impacts on drug metabolism and toxicity will not only facilitate the way of personalized medicine, but also improve rational drug design.
This review provides an overview of the microbiota-host co-metabolism on drug metabolism and summarizes 30 clinical drugs that are co-metabolized by host and gut microbiota. Moreover, this review is specifically focused on elucidating the gut microbial modulation of some clinical drugs, in which the gut microbial influences on drug metabolism, drug-induced toxicity and efficacy are discussed.
The gut microbial contribution to drug metabolism and toxicity is increasingly recognized, but remains largely unexplored due to the extremely complex relationship between gut microbiota and host. The mechanistic elucidation of gut microbiota in drug metabolism is critical before any practical progress in drug design or personalized medicine could be made by modulating human gut microbiota. Analytical technique innovation is urgently required to strengthen our capability in recognizing microbial functions, including metagenomics, metabolomics and the integration of multidisciplinary knowledge.
肠道微生物群在药物代谢中起关键作用。肠道微生物群的变化导致个体对药物治疗的差异,包括药物诱导的毒性和疗效。因此,研究和阐明肠道微生物对药物代谢和毒性的影响不仅有助于个性化医疗的发展,还能改进合理的药物设计。
本综述概述了微生物群与宿主的共同代谢对药物代谢的影响,并总结了30种由宿主和肠道微生物群共同代谢的临床药物。此外,本综述特别关注阐明肠道微生物对某些临床药物的调节作用,其中讨论了肠道微生物对药物代谢、药物诱导的毒性和疗效的影响。
肠道微生物对药物代谢和毒性的贡献越来越受到认可,但由于肠道微生物群与宿主之间极其复杂的关系,这方面仍在很大程度上未被探索。在通过调节人类肠道微生物群实现药物设计或个性化医疗的任何实际进展之前,阐明肠道微生物群在药物代谢中的机制至关重要。迫切需要分析技术创新来增强我们识别微生物功能的能力,包括宏基因组学、代谢组学以及多学科知识的整合。