Dietary Microplastics Engage Gut Mechanosensory-Endocrine Signaling and Disrupt Bone Homeostasis
Year: 2026
Type: preprint
Abstract: Background and Aims Microplastics are pervasive environmental contaminants increasingly detected in food and water supplies; however, their effects on gastrointestinal physiology and systemic health remain poorly understood. We investigated whether chronic dietary microplastic exposure alters colonic neuroendocrine signaling and skeletal health. Methods 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 (∼1.7 mg/kg; particle sizes 0.49 – 5.0 µm) 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. Results 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. Conclusions 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.
Authors: Aaron S. Romero, Sumira Phatak, Sanchiti Patil, Hamid Y. Dar, Jaclyn A. Rivas, Olufunmilola M Oyebamiji, Brianna B. Maes, Siem S. Goitom, Crystal Madera Enriquez, Jazmin Orozco, Cristina N. Coffman, Ruixuan Liu, Julie G. In, Matthew J. Campen, Kel Cook, Richard Levenson, Jessica M. Gross, Shuguang Leng, Anthony Cretara, Roberto Pacifici, Eliseo F. Castillo
Language: English
Subfield: Pollution
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
Awards: G10775630, G1849608474, G2211972217, G4709510759, G4718495392, G4745244241, G77486010, Academic Science Education and Research Training, University of New Mexico Center for Metals in Biology and Medicine, University of New Mexico Cancer Center Support Grant, Autophagy, Inflammation and Metabolism (AIM) in Disease Center - Phase 2., G951575394, G962487624
OpenAlex ID: W7151321069