Toxicological assessments based on intestine 3D organoids reveal environmental low-dose nanosized microplastics (NPs) exposure aggravates radiation-induced intestine injury

BACKGROUND: Intestinal organoid has emerged as an energetic tool for modeling intestine physiology and relevant diseases in vitro. Here, we reported that development of intestinal organoids could be used to explore the toxicology mechanism for combination effects of low dose nanoplastic (NPs) chronic exposure and acute radiation on intestine injury, the two classical chemical and physical substances. METHODS: Integrated acute radiation-induced intestine injury model in vivo and mice intestinal organoids in vitro were conducted in this study. RESULTS: First, through in vivo study, we found low dose NPs exposure could aggravate acute radiation-induced intestine injury including exacerbating damaged intestinal epithelial structure, shortened and fractured intestinal villi. Second, using an intestinal organoid model, we observed that low-dose NPs reduced radiation-induced proliferation and exacerbated inflammatory damage, which promoted inflammatory damage through elevated TGF-β1 expression, increased Smad3 phosphorylation, and diminished Smad7 expression. Furthermore, immunohistochemical and Western blot analyses of intestinal tissues further confirmed that low-dose nanoplastics enhance radiation-induced intestinal damage via activation of the TGF-β1/p-Smad3 signaling pathway. CONCLUSION: This study demonstrates that low-dose NPs may exacerbate the radiation-induced intestinal damage and inflammation process in vivo and in vitro. Our study highlights, for the first time, the potential for intestine organoids serving as powerful tool for explore the combination effects of two chemical and physical substances in toxicology investigation.