title: Targeting the human genome-microbiome axis for drug discovery: inspirations from global systems biology and traditional Chinese medicine.
abstract: Most chronic diseases impairing current human public health involve not only the human genome but also gene-environment interactions, and in the latter case the gut microbiome is an important factor. This makes the classical single drug-receptor target drug discovery paradigm much less applicable. There is widespread and increasing international interest in understanding the properties of traditional Chinese medicines (TCMs) for their potential utilization as a source of new drugs for Western markets as emerging evidence indicates that most TCM drugs are actually targeting both the host and its symbiotic microbes. In this review, we explore the challenges of and opportunities for harmonizing Eastern-Western drug discovery paradigms by focusing on emergent functions at the whole body level of humans as superorganisms. This could lead to new drug candidate compounds for chronic diseases targeting receptors outside the currently accepted "druggable genome" and shed light on current high interest issues in Western medicine such as drug-drug and drug-diet-gut microbial interactions that will be crucial in the development and delivery of future therapeutic regimes optimized for the individual patient.
authors.affiliation: Shanghai Center for Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. lpzhao3517@gmail.com
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jia V
authors.initials: JV
authors.lastname: Li
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
mesh_terms: D000818:Animals; D002908:Chronic Disease / Q000188:drug therapy; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D041981:Gastrointestinal Tract / Q000382:microbiology; D015894:Genome, Human; D006801:Humans; D008516:Medicine, Chinese Traditional; D054892:Metagenome / Q000187:drug effects; D049490:Systems Biology
chemical_list: D004365:Drugs, Chinese Herbal