Industrial and agricultural chemicals exhibit antimicrobial activity against human gut bacteria in vitro

Industrial and agricultural chemicals such as pesticides are often considered to have restricted biological activity. Yet, there are concerns regarding their broader toxicity range and impact on human gut microbiota. Here we report a systematic in vitro screening to assess the impact of 1,076 pollutants, spanning diverse chemistries and indicated applications, on 22 prevalent gut bacteria. Our investigation uncovered 588 inhibitory interactions involving 168 chemicals, the majority of which were not previously reported to have antibacterial properties. Fungicides and industrial chemicals showed the largest impact, with around 30% exhibiting anti-gut-bacterial properties. We demonstrate that the scale of our dataset enables a machine learning approach for predicting the antibacterial activity of pesticides. Mechanistically, chemical-genetic screens using transposon mutant libraries of Parabacteroides merdae and Bacteroides thetaiotaomicron implicated genes involved in conserved efflux pathways, including the acrR locus, as mediators of pollutant resistance. We also found that loss-of-function mutations in genes coding for metabolic enzymes were selected under pollutant exposure, including those for branched short-chain fatty acid biosynthesis under tetrabromobisphenol A, a flame retardant. Taken together, our results suggest that the antibacterial activity of chemical pollutants should be considered in future studies on the microbiome and the emergence of antimicrobial resistance, as well as in toxicological assessments.