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.
Keywords: Microbiome; Pesticides; Polyamines; Stress Response; Xenobiotics.
© 2025. The Author(s).