Role of Gut Microbiota in Chemical Toxicity
A large portion of the genes expressed in humans come from the microbes colonizing our bodies and the microbiome has emerged as a regulator of disease. The human gut is home to a diverse community which, through the functionality of microbial genes, can block or activate adverse effects of drugs, and food and environmental chemicals. Growing knowledge suggests a need to re-evaluate chemical safety to account for the impact of gut microbial influences. Our research at the intersection of gut microbiota and toxicity is motivated by the concept of biomarker-based strategies for predicting how human gut microbiota influence individual susceptibility to the effects of chemicals and drugs. Our work entails identifying chemical and biological mechanisms by which chemicals bioavailable in the colon are transformed by gut microbiota and how the resulting structural changes alter toxicity. We characterize the capacity of various strains of commensal gut bacteria as well as complex human gut microbial communities to transform toxicants, identify the chemical structures of metabolites and their mechanism of formation, and evaluate the impact of the transformation on toxic potency. This research is enabled by collaboration between the ETH Laboratories of Toxicology and Food Biotechnology, and utilizes state-of-the-art techniques, such as continuous in vitro gut fermentation models, stable isotope tracer bioanalysis methods, and in vitro human cell-based models.
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