National Laboratory Animal Center, National Applied Research Laboratories, Taipei City 115021, Taiwan.
Department of Life Sciences, National Central University, Taoyuan, Taiwan.
Ecotoxicol Environ Saf. 2024 Nov 1;286:117171. doi: 10.1016/j.ecoenv.2024.117171. Epub 2024 Oct 12.
Ambient fine particulate matter (PM), a vital environmental toxicant, not only adversely affects the cardiovascular and respiratory systems but also potentially exhibits an association with intestinal inflammation and colorectal cancer (CRC). The underlying molecular mechanisms of PM2.5 impacts on CRC are still unclear. In this study, we utilized collected ambient PM and standard reference material SRM2786 to investigate the toxic effects on the colon through in vivo chronic exposure mouse and in vitro cell culture models. We employed a chronic mouse exposure model to clarify the colonic injury and gut microbiome biomarkers. Prolonged exposure to PM via oropharyngeal aspiration led to a significant rise in colonic epithelial proliferation and reduced colon length in mice. It triggered characteristics indicative of gut microbiota dysbiosis linked to inflammatory bowel disease. The gut microbiome alternations may serve as a biomarker indicating the colonic health impacts of PM exposure. PM and SRM2786-induced cytotoxicity manifested as autophagy dysregulation-mediated abnormal proliferation, IL-8 production, p62/SQSTM1 accumulation, and lysosomal membrane damage in human colon cells WiDr and Caco-2. Both PM and SRM2786 exposures led to the accumulation of p62/SQSTM1 and compromised lysosomal membrane integrity, showing impaired autophagic flux in WiDr and Caco-2 cells. Finally, we examined the correlations between atmospheric PM data and biomarkers of colonic inflammation in human population. The serum level of IL-8 was significantly correlated with regional anthropogenic pollutants. In conclusion, our findings elucidate that ambient PM exhibits adverse effects on colon health manifested as inflammation, aberrant proliferation, and gut dysbiosis, potentially mediated through autophagy dysregulation, thereby highlighting the importance of further research on the impact of environmental pollutants on gastrointestinal health.
环境细颗粒物（PM）是一种重要的环境毒物，不仅对心血管和呼吸系统有不良影响，而且还可能与肠道炎症和结直肠癌（CRC）有关。PM2.5 对 CRC 的影响的潜在分子机制尚不清楚。在这项研究中，我们利用收集到的环境 PM 和标准参考物质 SRM2786，通过体内慢性暴露小鼠和体外细胞培养模型来研究 PM 对结肠的毒性作用。我们采用慢性小鼠暴露模型来阐明结肠损伤和肠道微生物组生物标志物。通过口咽吸入的方式长时间暴露于 PM 会导致结肠上皮细胞增殖显著增加，结肠长度缩短。这引发了与炎症性肠病相关的肠道微生物群失调的特征。肠道微生物群的改变可能作为指示 PM 暴露对结肠健康影响的生物标志物。PM 和 SRM2786 诱导的细胞毒性表现为自噬失调介导的异常增殖、IL-8 产生、p62/SQSTM1 积累和溶酶体膜损伤，在人结肠细胞 WiDr 和 Caco-2 中。PM 和 SRM2786 暴露均导致 p62/SQSTM1 积累和溶酶体膜完整性受损，显示 WiDr 和 Caco-2 细胞中的自噬流受损。最后，我们检查了大气 PM 数据与人群中结肠炎症生物标志物之间的相关性。IL-8 的血清水平与区域人为污染物显著相关。总之，我们的研究结果表明，环境 PM 对结肠健康表现出不良影响，表现为炎症、异常增殖和肠道菌群失调，可能通过自噬失调介导，从而强调了进一步研究环境污染物对胃肠道健康影响的重要性。
