Abstract
The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter- and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification. As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities. Xenobiotic-microbiome relationships are mutual and dynamic. Not only does the human microbiome have a direct metabolizing potential on xenobiotics, but it can also influence the expression of the host metabolizing genes and the activity of host enzymes. On the other hand, xenobiotics may alter the microbiome composition, leading to a state of dysbiosis, which is linked to multiple diseases and adverse health outcomes, including increased toxicity of some xenobiotics. Toxicomicrobiomics studies these mutual influences between the ever-changing microbiome cloud and xenobiotics of various origins, with emphasis on their fate and toxicity, as well the various classes of microbial xenobiotic-modifying enzymes. This review article discusses classic and recent findings in toxicomicrobiomics, with examples of interactions between gut, skin, urogenital, and oral microbiomes with pharmaceutical, food-derived, and environmental xenobiotics. The current state and future prospects of toxicomicrobiomic research are discussed, and the tools and strategies for performing such studies are thoroughly and critically compared.
Highlights
Specialty section: This article was submitted to Predictive Toxicology, a section of the journal Frontiers in Pharmacology
The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter- and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification
As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities
Summary
Xenobiotics are chemical substances not normally present in the environment of living organisms. They can be defined as chemicals that are extrinsic to the normal metabolism of a living organism (Koppel et al, 2017). Food with its variety of dietary compounds, environmental chemicals and pollutants, as well as medications are considered xenobiotics to the human body (Koppel et al, 2017). Xenobiotic metabolism increases their water solubility, enhancing their elimination from the body (Clarke et al, 2019). The final fate of these metabolites is either excretion in the stool or reabsorption in the small intestine (Koppel et al, 2017)
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