荷兰鹿特丹大学医学中心Cornelia M. van Duijn和Jun Liu研究组合作将流行病学、药理学、遗传和肠道微生物数据整合在一个药物代谢物图谱中。相关论文在线在2020年1月13日的《自然—医学》上。

横断面研究显示他汀类药物对代谢物的作用评估与干预和遗传观察研究的作用评估具有可比性。进一步的数据整合将质子泵抑制剂与循环代谢物、肝功能、肝脂肪变性和肠道微生物组联系起来。他们的图谱为靶向实验性药物研究和临床试验提供了工具，以提高药物功效、安全性和用途。他们提供了一个基于Web的资源来可视化图谱(http://bbmri.researchlumc.nl/atlas/)。

据了解，高通量代谢谱分析的进展为了解药物对人类代谢的影响提供了前所未有的机会。荷兰的生物银行生物分子研究基础设施通过质子核磁共振评估了87种常用处方药和150种临床相关的血浆代谢物，建立了药物代谢物关联图集。该图集包括对十个队列（18,873人）的元分析，并在评估混杂因素（包括联合治疗）后发现1,071个药物-代谢物关联。

附：英文原文

Title: Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug–metabolite atlas

Author: Jun Liu, Lies Lahousse, Michel G. Nivard, Mariska Bot, Lianmin Chen, Jan Bert van Klinken, Carisha S. Thesing, Marian Beekman, Erik Ben van den Akker, Roderick C. Slieker, Eveline Waterham, Carla J. H. van der Kallen, Irene de Boer, Ruifang Li-Gao, Dina Vojinovic, Najaf Amin, Djawad Radjabzadeh, Robert Kraaij, Louise J. M. Alferink, Sarwa Darwish Murad, Andr G. Uitterlinden, Gonneke Willemsen, Rene Pool, Yuri Milaneschi, Diana van Heemst, H. Eka D. Suchiman, Femke Rutters, Petra J. M. Elders, Joline W. J. Beulens, Amber A. W. A. van der Heijden, Marleen M. J. van Greevenbroek, Ilja C. W. Arts, Gerrit L. J. Onderwater, Arn M. J. M. van den Maagdenberg, Dennis O. Mook-Kanamori, Thomas Hankemeier, Gisela M. Terwindt, Coen D. A. Stehouwer, Johanna M. Geleijnse, Leen M. t Hart, P. Eline Slagboom, Ko Willems van Dijk, Alexandra Zhernakova, Jingyuan Fu, Brenda W. J. H. Penninx, Dorret I. Boomsma, Aye Demirkan, Bruno H. C. Stricker, Cornelia M. van Duijn

Issue&Volume: 2020/01/13

Abstract: Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drugmetabolite associations for 87commonly prescribed drugs and 150clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873persons) and uncovers 1,071drugmetabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (http://bbmri.researchlumc.nl/atlas/). Comprising data from over 18,000 people, a new atlas of drugmetabolite associations for 87commonly prescribed drugs and 150metabolites assessed by proton nuclear magnetic resonance provides a web-based tool to aid research on drug efficacy, safety and repurposing.

DOI: 10.1038/s41591-019-0722-x

Source:https://www.nature.com/articles/s41591-019-0722-x