Multiomics Reveals Nonphagocytosable Microplastics Induce Colon Inflammatory Injury via Bile Acid-Gut Microbiota Interactions and Barrier Dysfunction.

Abstract

Microplastics (MPs), as emerging global environmental pollutants, exhibit intestinal toxicity mechanisms that are closely associated with the particle size. Nonphagocytosable MPs (NPMs), though incapable of being internalized by intestinal epithelial cells, still provoke colonic inflammatory damage. However, the exact mechanisms remain elusive. This study established a BALB/c mouse model subjected to long-term oral exposure to 10 μm polystyrene MPs (PS MPs) to comprehensively explore how NPMs induce colonic inflammation and injury. The results demonstrate that prolonged PS MPs exposure disrupts the colonic redox balance, leading to oxidative stress. Simultaneously, it disturbs intestinal immune homeostasis by elevating the Th17/Treg cell ratio and upregulating pro-inflammatory cytokines. Additionally, PS MPs notably compromise intestinal mechanical barrier function, diminishing mucin secretion and downregulating tight junction protein expression. Multiomics analysis further uncovered that PS MPs induce bile acid (BA) metabolic dysregulation by interfering with liver function and gut microbiota, causing a marked accumulation of total bile acids in the colon, especially conjugated BAs. Both in vitro and in vivo experiments confirmed that specific concentrations of taurochenodeoxycholic acid (TCDCA) activate the reactive oxygen species-mitochondrial pathway, triggering apoptosis in colonic epithelial cells and exacerbating PS MPs-induced colonic inflammatory injury. This study provides the first evidence of a cross-organ regulatory mechanism in which NPMs mediate intestinal toxicity via the "liver-BA-gut axis," offering novel theoretical insights for assessing the intestinal toxicity of MPs.