Microplastic exposure is associated with enhanced PI3K-Akt signaling in DSS-induced colitis: integrated bioinformatics analyses and in vivo validation

Abstract

Background Microplastics (MPs) are widely distributed in the environment and may aggravate ulcerative colitis (UC), but the underlying molecular mechanisms remain unclear. Methods We integrated network toxicology, RNA-seq-based differential expression analysis, molecular docking, GeneMANIA-based functional association analysis, and experimental validation in a murine DSS-induced colitis model. Results We identified 421 MP-related and 6,452 UC-related targets, including 265 overlapping targets. PIK3CD, PIK3CA, SRC, PTPN11, and EGFR were prioritized as hub targets with stable ligand binding. Enrichment analyses implicated the PI3K-Akt, JAK-STAT, T-cell receptor, and HIF-1 signaling pathways. In vivo experiments showed that MP exposure increased the colonic abundance of these five proteins and enhanced p-PI3K and p-AKT signals in DSS-induced colitis. Conclusion MP exposure is associated with enhanced PI3K-Akt signaling in experimental colitis. These findings provide preliminary biological support for the PI3K-Akt pathway as a potentially relevant mechanism linking MP exposure to UC aggravation.