118 Heat-treated PTFE nanoplastics cause chronic colon inflammation in mice

Abstract Polytetrafluoroethylene (PTFE) nanoplastics released from non-stick PTFE cookware during cooking may represent an overlooked dietary exposure risk to gut health. To address this, we exposed female C57BL/6 mice to an oral gavage of 20 mg/kg bw with four PTFE particles: P1 (30 to 50 nm), its heat-treated form P1-H, P2 (100 to 150 nm) and its corresponding heat-treated P2-H. Jejunal, colonic, and mesenteric lymph nodes (MLN) responses were assessed over 28 d after exposure using transcriptional, histological, and immunological analyses. In the jejunum, P1-H induced the strongest early epithelial response, characterised by Nlrp3-associated inflammation and mucosal remodelling with increased goblet cells and Muc1 expression on Day 1, which resolved by Day 28. In contrast, the distal colon showed sustained inflammation: P1 and P2 produced the highest pro-inflammatory cytokine activity on Day 7, and P2-H drove the strongest response on Day 28 with elevated Tnf-α and Il-6 expression. Mechanistically, the MLNs recognised P1-H earliest at Days 1 and 7, as shown by increases in monocytes and CD4⁺ T cells, which align with its early jejunal response and the much weaker inflammation that later appeared in the distal colon. Conversely, P1, P2 and P2-H showed delayed MLN involvement, which aligned with the pattern of chronic distal colon inflammation on day 28: moderate with P1, more pronounced with P2 and most persistent with P2-H. Our findings establish heat-treated PTFE nanoplastics (>100 nm) as a serious gastrointestinal hazard arising from routine cooking with non-stick cookware, warranting further evaluation to update safety standards for PTFE-coated cookware.