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

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.