Oral Ingestion of Polystyrene Microplastics Aggravates Chronic Pancreatitis Through <scp>ROS</scp> Induced <scp>NF</scp> ‐κb/ <scp>TGF</scp> ‐β Signaling Pathway and Alteration of Gut Microbiota

Microplastics (MPs), as a kind of emerging pollutant, have attracted widespread attention. The effects of MPs of different diameter sizes on chronic pancreatitis and their underlying mechanisms remain to be explored. Therefore, we established a mouse chronic pancreatitis model exposed to two-diameter polystyrene particles (2 or 0.5 μm) for 6 weeks. We found that MPs exposure resulted in severe pancreatic fibrosis in mice, which was negatively correlated with particle size. In-depth mechanistic exploration revealed that after exposure to MPs, MPs can enter pancreatic stellate cells through the cell membrane, stimulate the activation of cellular ROS, further activate the NF-κB and TGF-β signaling pathways, and increase the levels of fibrotic proteins and collagen. The pancreatic fibrosis can be reversed by the ROS inhibitor N-acetyl cysteine (NAC). Meanwhile, oral intake of polystyrene particles in chronic pancreatic mice also affected the diversity of intestinal bacteria, downregulating the bacteria in the Bacteroidota phylum and upregulating the bacteria in the Verrucomicrobiota phylum, which could be another potential mechanism underlying the pathogenic effect of pancreatic fibrosis. Our findings reveal the adverse effects of MPs on chronic pancreatitis through inducing cellular ROS, activating pancreatic stellate cells and altering gut microbes.