02470nas a2200349   4500000000100000000000100001008004100002260001200043653002100055653002300076653001700099100001500116700002000131700002200151700001400173700001900187700001300206700001400219700001600233700001800249700002200267700002700289700001500316700001900331700001900350245010900369856005500478300001400533490000700547520155200554022001402106       2025                            d  c2025-1210aChemical biology10aMicrobial genetics10aMicrobiology1 aIndra Roux1 aAnna E. Lindell1 aAnne Grießhammer1 aTom Smith1 aShagun Krishna1 aRui Guan1 aDeniz Rad1 aLuisa Faria1 aSonja Blasche1 aKaustubh R. Patil1 aNicole C. Kleinstreuer1 aLisa Maier1 aStephan Kamrad1 aKiran R. Patil00aIndustrial and agricultural chemicals exhibit antimicrobial activity against human gut bacteria in vitro  uhttps://www.nature.com/articles/s41564-025-02182-6  a3107-31210 v103 aIndustrial 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.  a2058-5276