Colonic Barrier Dysfunction and Inflammation Induced by Nano‐/Micro‐Plastics Fibers in Mice via the FAK/NF‐κB/iNOS and TLR4/NF‐κB/iNOS Pathways

ABSTRACT As emerging environmental contaminants, nano‐ and micro‐plastics (NMPs) have drawn increasing research attention due to potential hazards to organisms. Particle shape is a key factor influencing the toxic effects of NMPs, and NMPs of different shapes cause varying degrees of tissue damage. We investigated the specific mechanisms of polystyrene NMPs (PS‐NMPs) with different shapes underlying damage to the colonic intestinal barrier. We divided 120 five‐week‐old male C57BL/6J mice into seven groups that were orally exposed to different doses of PS‐NMPs for 5 weeks. Hematoxylin and eosin staining showed that both shapes of PS‐NMPs induced colon pathological injuries, with more pronounced damage in the PS‐Fibers groups. DAO and D‐LA levels were increased in the medium‐ and high‐dose groups. In all PS‐Fibers groups, DAO and D‐LA levels were significantly elevated. Immunohistochemical analysis revealed discontinuous distribution and reduced expression of ZO‐1 and occludin in the PS‐NMPs groups. Alcian blue‐periodic acid–Schiff staining results indicated that both types of PS‐NMPs significantly reduced the number of goblet cells. The levels of ZO‐1, occludin, MUC2, and E‐cadherin were significantly decreased in the high‐dose PS‐Beads group and all PS‐Fibers groups. The expression of pro‐inflammatory cytokines was significantly increased in the high‐dose PS‐Beads group and all PS‐Fibers groups. Mechanistically, PS‐Fibers induced colonic intestinal barrier damage by activating both the TLR4/NF‐κB/iNOS and FAK/NF‐κB/iNOS pathways, whereas PS‐Beads induced damage primarily via the TLR4/NF‐κB/iNOS pathway. These findings highlight the effect of differently shaped PS‐NMPs on affecting colonic barrier function, thereby providing new insights into the adverse health effects of NMPs.