Capacity of the Human Gut Microbiome in Metabolism of Drugs and Its Interaction with CYP450 Enzymes

Abstract

As a promising field of pharmaceutical sciences, gut microbiome effects on metabolism of xenobiotics, has shown great potential to be considered as a milestone. Xenobiotic chemistries are modified by some drug metabolizing enzymes in gut microbiome which are mostly unknown, however their functionality and the way they impose changes on drug structures are well known. Most of the drug metabolizing enzymes in gut microbial population have reductor effects which are in contrary to the host metabolic system with oxidative reactions. Hydrolysis and transfer of functional groups such as methyl, amine, hydroxyl and carboxyl also bring changes in the structure of xenobiotics. In this brief review, some of these changes on the structure of some important drugs and endogenous compounds have been mentioned, however, illustration of the complete picture has limitations. Furthermore, the significant regulatory role of metabolites generated from the function of gut microbiome enzymes on the expression and activity of host CYP450 enzymes are briefly discussed. Mostly, these effects are inhibitory and are imposed on the expression and activity of nuclear receptor transcription factors including Active/Androgen Receptors (CAR), Pregnane X-Receptors (PXR), Farnesoid X receptor (FXR) and Aryl Hydrocarbon Receptor (AHR).