Chlorpyrifos modulates the mouse gut microbiota and metabolic activity

The organophosphate chlorpyrifos is a commonly used pesticide for fruits and vegetables despite its association with neurotoxicity in humans. While some studies suggest that organophosphates may impact the gut microbiota, no studies to date have investigated the direct effect of chlorpyrifos on the gut microbiota with doses that approximate environmentally relevant dietary concentrations (EPA chronic reference dose: 0.3 µg/kg/day in humans and EPA acute reference dose: 5 µg/kg/day in humans). Thus, we examined the influence of chlorpyrifos on the gut microbiota by assessment of bacterial physiology and metabolism using flow cytometry, 1H NMR-based metabolomics, and changes in the cecal microbiota community with 16S rRNA amplicon sequencing and analysis. Chlorpyrifos did not directly damage bacteria but rather perturbed bacterial metabolism. Chlorpyrifos exposure to bacteria increased the concentration of amino acids, carbohydrates, and nucleic acids. The relative abundances of Lactobacillus, Allobaculum, Roseburia, and Butyricicoccus increased after exposure to chlorpyrifos. Analyses of the 16S rRNA gene amplicon data predicted decreased amino acid biosynthesis and nucleic acid degradation and increased glycolysis which was supported by 1H NMR-based metabolomics. Collectively, these results demonstrate that environmentally relevant doses of chlorpyrifos can impact the metabolic activity of isolated gut microbes which may result in an imbalance in overall gut metabolic activity.