Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine

Authors: Starke-Reed, Pamela; KHALSA, JAG - National Institutes Of Health (NIH); DUFFY, LINDA - National Institutes Of Health (NIH); HUBBARD, VAN - National Institutes Of Health (NIH); RISCUTA, GABRIELA - National Institutes Of Health (NIH)

Submitted to: Clinical Pharmacology in Drug Development (CCDD)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2016
Publication Date: 3/1/2017
Citation: Starke-Reed, P.E., Khalsa, J., Duffy, L.C., Hubbard, V.S., Riscuta, G. 2017. Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine. Clinical Pharmacology in Drug Development. 6(2):176-185.

Interpretive Summary: 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. Gut microbiota, 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 influence individual variation in drug response. In addition, some microbiota-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-microbiota 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 [Personalised] Medicine. A new perspective of gut-liver-metabolic interactions is emerging on understanding the effect of gut microbiota on human response to drugs, as an indispensable step toward providing precision therapies that would be more efficient, cost-effective, and with lower adverse events.

Technical 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. Gut microbiota, 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 influence individual variation in drug response. In addition, some microbiota-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-microbiota 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 [Personalised] Medicine. A new perspective of gut-liver-metabolic interactions is emerging on understanding the effect of gut microbiota on human response to drugs, as an indispensable step toward providing precision therapies that would be more efficient, cost-effective, and with lower adverse events.