Dmd065714 1499..1504

The importance of the gut microbiome in determining not only overall health, but also in the metabolism of drugs and xenobiotics, is rapidly emerging. It is becoming increasingly clear that the gut microbiota can act in concert with the host cells to maintain intestinal homeostasis, cometabolize drugs and xenobiotics, and alter the expression levels of drug-metabolizing enzymes and transporters and the expression and activity levels of nuclear receptors. In this myriad of activities, the impact of the microbiota may be beneficial or detrimental to the host. Given that the interplay between the gut microbiota and host cells is likely subject to high interindividual variability, this work has tremendous implications for our ability to predict accurately a particular drug’s pharmacokinetics and a given patient population’s response to drugs. In this issue of Drug Metabolism and Disposition, a series of articles is presented that illustrate the progress and challenges that lie ahead as we unravel the intricacies associated with drug and xenobiotic metabolism by the gut microbiota. These articles highlight the underlying mechanisms that are involved and the use of in vivo and in vitro approaches that are currently available for elucidating the role of the gut microbiota in drug and xenobiotic metabolism. These articles also shed light on exciting new avenues of research that may be pursued as we consider the role of the gut microbiota as an endocrine organ, a component of the brain-gut axis, and whether the gut microbiota is an appropriate and amenable target for new drugs.