INTRODUCTION: Our microbiome harbours a metabolic capacity far beyond our own. Moreover, its gene pool is highly adaptable and subject to selective pressure, including host exposure to xenobiotics. Yet, the resulting adaptations do not necessarily follow host well-being and can therefore contribute to disease or unfavourable metabolite production. AREAS COVERED: This review provides an overview of our host-microbiome relationship in light of bacterial (xenobiotic) metabolism, community dynamics, entero-endocrine crosstalk, dysbiosis and potential therapeutic targets. In addition, it will highlight the need for a systematic analysis of the microbiome's potential for substance toxification. EXPERT OPINION: The influence of our microbiota reaches from primary metabolites to secondary effects such as substrate competition or the activation of eukaryotic Phase I and Phase II enzymes. Further on it plays a hitherto underestimated role in drug metabolism, toxicity and pathogenesis. These effects are partly caused by entero-endocrine crosstalk and interference with eukaryotic regulatory networks. On first sight, the resulting concept of a metabolically competent microbiome adds enormous complexity to human physiology. Yet, the potential specificity of microbial targets harbours therapeutic promise for diseases such as diabetes, cancer and psychiatric disorders. A better physiological and biochemical understanding of the microbiome is thus of high priority for academia and biomedical research.