Oral administration of polystyrene microplastics for 2 weeks induces chronic constipation in ICR mice

Abstract Objective: Indirect evidence has determined the possibility that microplastics (MP) induce constipation, although direct scientific proof for constipation induction in animals remains unclear. Thus, this study is aimed to investigate whether oral administration of polystyrene MP causes constipation.Methods: An alteration in the constipation parameters and their molecular mechanisms was analyzed in ICR mice treated with 0.5 μm polystyrene (PS)-MP for 2 weeks. Results: Significant alterations in water consumption, stool weight, stool water contents, and stool morphology were detected in MP treated ICR mice, as compared to Vehicle treated group. Also, the gastrointestinal (GI) motility and intestinal length were decreased, while the histopathological structure and cytological structure of the transverse colon were remarkably altered in treated mice. Mice exposed to MP also showed a significant decrease in the GI hormone concentration, muscarinic acetylcholine receptors (mAChRs) expression and their downstream signaling pathway, as well as mucin secretion and transcription of the MUC1, MUC2 and Klf4 genes. Subsequent to MP treatment, concentrations of chloride ion and expressions of its channel (CFTR and CIC-2) were decreased, whereas expressions of AQP3 and 8 for water transportation were downregulated by activation of the MAPK/NF-kB signaling pathway. These regulation on water and chloride transportation were verified in intestinal epithelioid cell line (IEC18) after MP treatment. Conclusion: These results are the first to suggest that oral administration of PS-MP induces chronic constipation through the dysregulation of GI motility, mucin secretion, and chloride ion and water transportation in the transverse colon.