Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage

作者：Shan Tian, Ruixue Li, Jiao Li, Jinhui Zou · 发表于：Environment International · 年份：2025 · DOI：10.1016/j.envint.2025.109258 · 被引用次数：43 · 研究领域：Microplastics and Plastic Pollution

Nanoplastics (NPs) have attracted widespread attention owing to their presence in the body. Recent studies highlighted the detrimental effects of NPs on the digestive tract. However, no studies have reported an association between NPs exposure and colitis-associated cancer (CAC). An azoxymethane/dextran sodium sulfate-induced CAC model was used, and polystyrene nanoparticles (PS-NPs) were selected for long-term exposure. Non-targeted metabolomics and 16S rRNA sequencing were used to detect changes in colonic metabolites and gut microbes following PS-NPs exposure. A lipopolysaccharide (LPS)-treated cancer cell model (Caco-2) exposed to PS-NPs was used to investigate the underlying molecular mechanism. Compared to the normal control group, mice in the PS-NPs group exhibited more tumor nodes and reactive oxygen species (ROS), higher expression of pan-CK and Ki-67, and more severe DNA damage. 16S rRNA sequencing revealed that exposure to PS-NPs altered the abundance of Allobaculum and Lactobacillus, whereas metabolic analysis showed that the most significant metabolites were enriched mostly in fatty acid metabolism. Experiments in LPS intervened Caco-2 cells showed that exposure to PS-NPs led to lipid peroxidation, oxidative stress, and DNA damage in Caco-2. Exposure to PS-NPs activated the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway both in the AOM/DSS mouse model and cellular model. Key proteins involved in fatty acid metaboli...