title: Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine.
abstract: Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. The gut microbiome, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease. Gut bacterial communities directly metabolize certain drugs, reducing their bioavailability and influencing individual variation in drug response. In addition, some microbiome-produced compounds may affect drug pharmacokinetics and pharmacodynamics via altered expression of metabolizing enzymes and drug transporters or genes coding for drug target proteins, drug response phenotypes, and disease states. Molecular-based high-throughput technologies are providing novel insight about host-gut microbiome interactions, homeostasis, and xenobiotic effects associated with wide variation in efficacy or toxicity in humans. It is envisioned that future approaches to treating and preventing liver disease will benefit from in-depth studies of the liver-microbiome axis. Thus, the microbiome shares a fundamental role in human physiology with various organ systems, and its importance must be considered in the rapid evolution of precision medicine. A new emerging perspective of understanding the effect of the gut microbiome on human response to drugs would be indispensable for developing efficacious, safe, and cost-effective precision therapies.
authors.affiliation: National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jag
authors.initials: J
authors.lastname: Khalsa
authors.affiliation: National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Duffy
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riscuta
authors.affiliation: Agricultural Research Service, United States Department of Agriculture, Washington, DC, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Starke-Reed
authors.affiliation: Formerly National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: Van S
authors.initials: VS
authors.lastname: Hubbard
mesh_terms: D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D064307:Microbiota; D004364:Pharmaceutical Preparations / Q000378:metabolism; D057285:Precision Medicine
chemical_list: D004364:Pharmaceutical Preparations
keywords: gut-liver-metabolic network; microbiome; omics; precision medicine; probiotics