The human gut microbiome contains a complex aggregate of colonic bacterial enzymes mediating the metabolism of a wide range of xenobiotics and dietary components. From a toxicology context, this presentation highlights examples of pre-systematic drug clearance mediated by colonic enzymes contributing to systemic metabolite exposure. In vitro and in vivo studies to provide mechanistic contributions of metabolite systemic exposure will be reviewed.
From a microbiome-based drug discovery context, this presentation will examine evidence of a causative link between dysbiosis and metabolic disorders. The functional roles of bacterial secondary metabolites such as short-chain fatty acids and branched-chain amino acids produced by colonic bacterial enzymes, and their roles in insulin signaling, intestinal incretin production and intestinal inflammation will be reviewed to highlight human gut microbiome-based research opportunities in T2DM, insulin resistance and obesity.
This presentation will conclude with an overview of established gut microbiome biomarkers and assay panels available to support investigations in understanding the metabolic fate of xenobiotics and colonic bacterial secondary metabolites.