药物代谢酶CYP3A在胆汁酸宿主-肠道微生物协同代谢中的生物学功能假说  

Potential roles of cytochrome P450 3A in host-gut microbial co-metabolism of bile acids

作　　者：兰轲[1] LAN Ke(West China School of Pharmacy,Sichuan University,Chengdu 610041,Sichuan Province,China)

机构地区：[1]四川大学华西药学院

出　　处：《中国临床药理学杂志》2019年第22期2923-2929,共7页The Chinese Journal of Clinical Pharmacology

摘　　要：药物代谢的生物学功能是药代动力学领域的基本科学问题之一,本世纪系统生物学的进展为该科学问题赋予了新的内涵。肠道菌群作为后天发育的器官与宿主存在密切的代谢相互作用;菌群合成的代谢物对宿主-微生物共生体是内源性的,但对宿主自身而言是后天发育且动态变化的"外源性"代谢物,这与药物的外源性属性非常类似。人类是否已进化出专门应对菌群代谢物的机制和系统,该系统是否正是我们所熟知的药物代谢系统?本文旨在抛砖引玉,以胆汁酸宿主-肠道微生物协同代谢网络中CYP3A4/3A7专属性催化的三级胆汁酸代谢通路为例,探讨CYP3A在胆汁酸宿主-肠道微生物协同代谢中的生物学功能,并展望本假说相关探索在精准医学时代临床药理研究中的广阔生命力。The biological function of drug metabolism is a fundamental scientific question in the field of drug metabolism and pharmacokinetics.In the post-genome era,the systems biology revealed key roles of host-intestinal microbial co-metabolism in health and diseases,which has enabled us to revisit the biological function of drug metabolism for precise medicine.As a postnatal acquired organ,the gut microbiota evolves intimate metabolic crosstalk with the host.Metabolites synthesized by bacteria are endogenous to the host-microbial symbiont,however,they are"exogenous"to the human body itself,which are very similar to the exogenous properties of drugs and xenobiotics.It’s therefore proposed that human genome has evolved a specific system in response to the"exogenous"metabolites synthesized by gut microbiota,and the specific system might be what we know as drug metabolism.Following our recently identified CYP3 A4/3 A7-catalyzed tertiary stereoselective oxidation pathways of deoxycholate species,this review aims to discuss potential roles of CYP3 A,the most important members of drug metabolizing enzymes,in the host-gut microbial co-metabolism of bile acids.Future basic and translational researches following this hypothesis is also prospected in the field of clinical pharmacology.

关 键 词：细胞色素P4503A 胆汁酸 宿主-肠道微生物协同代谢 生物学功能 药物代谢组学 

分 类 号：R97[医药卫生—药品]