和多醇基物质混合物通过微生物群衍生的21-脱氧皮质醇和皮质醇代谢失调破坏肠道屏障功能
Tingting Lin1, Luyang He2, Sishuo Liu3
1Institute of Environmental Medicine, Zhejiang University School of Public Health, Hangzhou 310058, China; Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China.
Journal of hazardous materials
|May 13, 2025
概括
和多醇基物质 (PFASs) 混合物通过改变肠道细菌和皮质醇水平来破坏大鼠的肠道屏障功能. 这会影响紧结蛋白质,突出显示环境污染物对肠道健康的风险.
科学领域:
- 环境毒理学环境毒理学
- 胃肠病学 胃肠病学
- 微生物组研究的研究.
背景情况:
- 和多基基物质 (PFAS) 是持久性污染物,具有已知的健康风险.
- 现实世界PFAS混合物对肠道健康的影响尚不清楚.
- 肠道疾病是与PFAS暴露相关的潜在健康后果.
研究的目的:
- 为了研究一种模仿群体的PFAS混合物对大鼠肠道平衡的作用.
- 阐明PFAS引起的肠道屏障破坏背后的机制.
- 探索肠道微生物组和代谢组在PFAS毒性的作用.
主要方法:
- 鼠被暴露在一种旨在模仿人类暴露的PFAS混合物中.
- 转录组分析被用来评估结肠中的基因表达变化.
- 免疫光学和免疫组织化学被用来评估紧结蛋白水平.
- 综合性分析连接了PFAS暴露,肠道微生物群变化和宿主代谢变化.
主要成果:
- PFAS混合物暴露导致了与细胞和紧密结合相关的基因的剂量依赖性改变.
- 关键紧结蛋白 (occludin,claudin-1) 在结肠表皮下降.
- PFAS破坏了肠道细菌 (例如,Ruminococcus),增加了21-脱氧皮质醇 (21-DF) 的产生.
- 升高的21-DF抑制了皮质醇转化,增加了皮质醇水平并抑制了紧密结合蛋白,从而损害了屏障功能.
结论:
- 在现实世界中,PFAS混合物通过肠道微生物组-代谢组-上皮细胞轴破坏肠道屏障功能.
- 这项研究揭示了一种涉及21-DF和皮质醇在PFAS诱导的肠道功能障碍中的新机制.
- 这些发现强调了在风险评估和干预中需要考虑复杂的污染物-微生物群-宿主相互作用的必要性.
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