Impact of drugs and environmental contaminants on amine production by gut bacteria

Xenobiotics like drugs are recognised as key influencers of gut bacterial growth. Yet, their impact on the production of metabolites involved in microbiota-host interactions is largely unknown. Here, we report the impact of commonly ingested xenobiotics-therapeutic drugs, pesticides, industrial chemicals, and sweeteners-on gut bacterial amine metabolism. We tested >13,000 interactions between >1700 compounds and 4 amine-producing bacteria, uncovering 747 xenobiotic-species-metabolite interactions involving 275 compounds. These compounds span all tested classes, with the majority being antimicrobial drugs. In 66% of the cases, amine production was correlated with growth, while the rest showed xenobiotic-induced decoupling between growth and metabolite production. The latter includes transient bursts in polyamine production by Escherichia coli in response to β-lactam antibiotics, and overproduction of aromatic amines by Ruminococcus gnavus treated with 15 diverse chemicals. Xenobiotics thus can disrupt metabolic homeostasis in both growth-dependent and -independent manner. We also find that metabolic responses have non-monotonic dose-dependency, resulting in lower doses sometimes having stronger effects. Our results bring forward the potential of common xenobiotics to disrupt the amine metabolism of gut bacteria.