Polystyrene nanoplastics trigger ferroptosis to aggravate ulcerative colitis: Integrated multi-database bioinformatics, machine learning, and experimental validation.

Polystyrene is a common pollutant in microplastics, which can enter the human body in many ways. At the same time, the incidence of ulcerative colitis (UC) has been rising, and there is evidence that it may be related to environmental factors. However, the specific association between PS-NPs exposure and ulcerative colitis, as well as the underlying biological mechanisms, remains poorly elucidated. By integrating multiple databases and the transcriptome data of GEO microplastics exposure research, we found the common difference targets related to polystyrene and UC, and then conducted functional enrichment analysis. We used different machine learning methods to screen hub genes, and used them to establish UC Risk Score. The prediction effect is verified by ROC curve analysis. Finally, we confirmed the mechanism of polystyrene nanoplastics (PS-NPs) in regulating UC through in vitro and in vivo experimental models. Five cross-genes (VCAM1, IL10, GPX3, GSTP1 and CAT) were identified, which are closely related to oxidative stress responses, glutathione metabolism and ferroptosis-related pathways. The risk prognostic model constructed based on these genes exhibits good predictive performance. In addition, laboratory and animal experiments have found that exposure to PS-NPs will make ulcerative colitis worse, which may be aggravated by ferroptosis signaling pathway. This study found five major genes related to microplastics's exposure and ulcerative colitis. These genetic markers have a strong relationship with ferroptosis and show high predictive value. Therefore, they can be used as effective diagnostic indicators and new treatment options for ulcerative colitis.