Ambient Particulate Matter Exposure Impairs Gut Barrier Integrity and Disrupts Goblet Cell Function.

: As a well-known environmental hazard, ambient fine particulate matter (PM, aerodynamic diameter ≤ 2.5 µm) has been positively correlated with an increased risk of digestive system diseases, including appendicitis, inflammatory bowel disease, and gastrointestinal cancer. Additionally, PM exposure has been shown to alter microbiota composition and diversity in human and animal models. However, its impact on goblet cells and gut mucus barrier integrity remains unclear. : To address this, 8-week-old male and female interleukin-10 knockout (IL10) mice, serving as a spontaneous colitis model, were exposed to concentrated ambient PM or filtered air (FA) in a whole-body exposure system for 17 weeks. Colon tissues from the PM-exposed mice and LS174T goblet cells were analyzed using H&E staining, transmission electron microscopy (TEM), and transcriptomic profiling. : The average PM concentration in the exposure chamber was 100.20 ± 13.79 µg/m. PM exposure in the IL10 mice led to pronounced colon shortening, increased inflammatory infiltration, ragged villi brush borders, dense goblet cells with sparse enterocytes, and lipid droplet accumulation in mitochondria. Similar ultrastructure changes were exhibited in the LS174T goblet cells after PM exposure. Transcriptomic analysis revealed a predominantly upregulated gene expression spectrum, indicating an overall enhancement rather than suppression of metabolic activity after PM exposure. Integrated enrichment analyses, including GO, KEGG, and GSEA, showed enrichment in pathways related to oxidative stress, xenobiotic (exogenous compound) metabolism, and energy metabolism. METAFlux, a metabolic activity analysis, further substantiated that PM exposure induces a shift in cellular energy metabolism preference and disrupts redox homeostasis. : The findings of exacerbated gut barrier impairment and goblet cell dysfunction following PM exposure provide new evidence of environmental factors contributing to colitis, highlighting new perspectives on its role in the pathogenesis of colitis.