Direct microbial interference with xenobiotics

Introduction The human body is home to a complex microbial ecosystem. The gastrointestinal tract houses the most numerous microbial community (the gut microbiota), consisting of approximately 1013 microbial cells (1). Collectively, the aggregate genomes of the gut microbiota encode more than 100 times as many unique genes as the approximately 20,000 protein-coding genes found in the human genome and nearly 20,000 gene families (2). Therefore it is not surprising that these genes and their encoded metabolic activities (the gut microbiome) expand host metabolic capabilities. In this Review, we focus on one particular area of critical relevance to clinical practice and investigation: the impact of the gut microbiome on xenobiotics, foreign compounds including therapeutic drugs and diet-derived bioactive compounds (Figure 1). We highlight key studies that illustrate the breadth of microbial influences and the diversity of mechanisms involved, while providing initial evidence that interindividual differences in the human gut microbiome contribute to variations in xenobiotic response. Finally, we discuss how this emerging area of study might be best leveraged to improve medicine in the coming years.