Gao Wanhao, Lin Wang, Tian Miao, Fan Shilang, Edwards Sabrina, Tran Joanne, Li Yuanjing, Rao Xiaoquan
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1195 Jiefang Ave, Wuhan 430030, China.
Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239, USA.
Biomedicines. 2025 Jul 25;13(8):1825. doi: 10.3390/biomedicines13081825.
: 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.
作为一种广为人知的环境危害物，环境细颗粒物（PM，空气动力学直径≤2.5微米）与消化系统疾病风险增加呈正相关，这些疾病包括阑尾炎、炎症性肠病和胃肠道癌症。此外，在人类和动物模型中，暴露于PM已被证明会改变微生物群的组成和多样性。然而，其对杯状细胞和肠道黏液屏障完整性的影响仍不清楚。
为了解决这个问题，将8周龄的雄性和雌性白细胞介素-10基因敲除（IL10）小鼠作为自发性结肠炎模型，在全身暴露系统中暴露于浓缩环境PM或过滤空气（FA）中17周。使用苏木精-伊红染色、透射电子显微镜（TEM）和转录组分析对暴露于PM的小鼠的结肠组织和LS174T杯状细胞进行分析。
暴露室中的平均PM浓度为100.20±13.79微克/立方米。IL10小鼠暴露于PM导致结肠明显缩短、炎症浸润增加、绒毛刷状缘参差不齐、杯状细胞密集而肠上皮细胞稀疏，以及线粒体中脂滴积累。PM暴露后，LS174T杯状细胞也表现出类似的超微结构变化。转录组分析显示基因表达谱主要上调，表明PM暴露后代谢活性总体增强而非抑制。包括基因本体（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）在内的综合富集分析表明，与氧化应激、异生物（外源化合物）代谢和能量代谢相关的通路富集。代谢活性分析METAFlux进一步证实，PM暴露会导致细胞能量代谢偏好发生转变并破坏氧化还原稳态。
PM暴露后肠道屏障损伤加剧和杯状细胞功能障碍的研究结果为环境因素导致结肠炎提供了新证据，突出了其在结肠炎发病机制中作用的新观点。
