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We investigated whether chronic dietary microplastic exposure alters colonic neuroendocrine signaling and skeletal health.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Female and male C57BL\/6J mice were fed purified basal, high-fat\/high-cholesterol, or high-fiber diets with or without a physiological relevant polystyrene microplastic mixture (\u223c1.7 mg\/kg; particle sizes 0.49 \u2013 5.0 \u00b5m) for 12 weeks. Colonic cellular responses were evaluated using ELISA, histology, immunofluorescence, and single-nuclei RNA sequencing. Fecal microbiota transplantation was performed to assess microbial contributions to microplastic-induced phenotypes. Bone microarchitecture was assessed by micro-computed tomography. Human bone specimens were analyzed for microplastic content, and primary osteoblast mineralization assays were performed.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Dietary microplastic exposure increased chromogranin A-positive enteroendocrine cells and enhanced serotonergic signaling in the colon without evidence of intestinal inflammation or lineage reprogramming. Single-nuclei transcriptomic analysis identified compartment-specific serotonergic and mechanosensory adaptations in epithelial and enteric neuronal populations. Transfer of microbiota from microplastic-exposed donors to control recipients recapitulated increased enteroendocrine cell abundance. Chronic microplastic ingestion induced sex- and diet-dependent reductions in trabecular bone loss and architecture without systemic inflammatory activation. Microplastics were detected in human mineralized bone, and microplastic exposure impaired osteoblast mineralization in a donor-dependent manner.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Chronic ingestion of microplastics remodels gut neuroendocrine signaling through microbiota-dependent mechanisms and impairs skeletal homeostasis in the absence of overt inflammation. These findings identify a previously unrecognized gut-bone pathway through which dietary microplastic exposure may influence host physiology.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.03.716216","type":"posted-content","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:25:20Z","timestamp":1775589920000},"source":"Crossref","is-referenced-by-count":0,"title":["Dietary Microplastics Engage Gut Mechanosensory-Endocrine Signaling and Disrupt Bone Homeostasis"],"prefix":"10.64898","author":[{"given":"Aaron S.","family":"Romero","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumira","family":"Phatak","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New 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