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Various subtypes of EECs produce distinct repertoires of monoamines and neuropeptides, which modulate intestinal motility and other physiologies. EECs also possess neuron-like properties, suggesting a potential vulnerability to ingested environmental neurotoxicants. One such group of toxicants is pyrethroids, a class of prevalent insecticides used residentially and agriculturally. Pyrethroids agonize voltage-gated sodium channels (VGSCs), inducing neuronal excitotoxicity, and affect the function of monoamine-producing neurons. Given their anatomical location at the interface with the environment and their expression of VGSCs, EECs likely represent a vulnerable cell type to oral pyrethroid exposure. In this study, we used the EEC cell line, STC-1 cells, to evaluate the effects of the common pyrethroid deltamethrin on the functional status of EECs. We find that deltamethrin impacts both the expression of serotonergic pathways and inhibits the adrenergic-evoked release of an EEC hormone, glucagon-like peptide 1, in vitro. In a mouse model of oral exposure, we found that deltamethrin induced an acute, yet transient, loss of intestinal motility in both fed and fasted conditions. This constipation phenotype was accompanied by a significant decrease in peripheral serotonin production and an inhibition of nutrient-evoked intestinal hormone release. Together, these data demonstrate that deltamethrin alters monoaminergic signaling pathways in EECs and regulates intestinal motility. This work demonstrates a mechanistic link between pyrethroid exposure and intestinal impacts relevant to pyrethroid-associated diseases, including inflammatory bowel disease, neurodegenerative disease, and metabolic disorders.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf076","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T07:54:26Z","timestamp":1750924466000},"page":"208-220","source":"Crossref","is-referenced-by-count":4,"title":["The pyrethroid insecticide deltamethrin disrupts neuropeptide and monoamine signaling pathways in the gastrointestinal tract"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-9868","authenticated-orcid":false,"given":"Alexandria C","family":"White","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine , Atlanta, GA 30322,","place":["United States"]},{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research 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