Enterohepatic circulation of nanoplastics induced hyperplasia, epithelial-mesenchymal transition, and neutrophil extracellular traps in gallbladder

Increasing concerns surround nanoplastic’s health risks owing to global exposure emphasize clear understanding of their dynamic distribution and organ-specific molecular effects. We assessed the health risks associated with nanoplastics (100 nm) following oral ingestion. Using a fluorescent tracking system, we demonstrated their recyclability through gastrointestinal tract-liver-gallbladder axis, with specific accumulation in the gallbladder. Pathological alterations in the gallbladder and single-cell RNA sequencing data indicated that short-term (three weeks) exposure induces gallbladder epithelial hyperplasia, whereas long-term exposure (six weeks) induces progressive hyperplasia, epithelial-mesenchymal transition (EMT), and fibrosis. Nanoplastic exposure facilitates neutrophil extracellular trap (NET) formation. Various nanoplastics were identified in human gallbladder bile samples using scanning electron microscopy (SEM) and Raman spectroscopy. Consistently, epithelial hyperplasia and neutrophil infiltration were observed in the gallbladder tissues, alongside nanoplastic detection in the bile. Our findings offer insights into the understanding of the enterohepatic-biliary recycling route of nanoplastics and their potential toxic consequences.