困难 Clostridioides 毒素改变宿主代谢途径和胆酸恒常基因表达在结肠表皮
Stephanie A Thomas1, Colleen M Pike2, Cypress E Perkins1
1Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Infection and immunity
|June 30, 2025
概括
抗生素的使用可以导致Clostridioides difficile感染 (CDI). 这项研究表明,CDI及其毒素破坏宿主胆固醇代谢和胆酸通路,影响肠道健康.
科学领域:
- 微生物学 微生物学
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
背景情况:
- 抗生素的使用破坏了肠道微生物群,增加了Clostridioides difficile感染 (CDI) 的风险.
- 困难菌的毒素 (TcdA,TcdB) 损害了肠道屏障并引起炎症.
- 在CDI期间了解宿主基因表达变化至关重要.
研究的目的:
- 为了研究宿主基因表达对C. difficile及其毒素的反应的变化.
- 为了识别代谢和炎症途径的变化.
- 探索对胆固醇和胆汁酸平衡的影响.
主要方法:
- 使用了一种用抗生素治疗的CDI小鼠模型.
- 使用NanoString Technologies的炎症基因面板分析了基因表达.
- 使用的Caco-2细胞培养和初级人类结肠上皮细胞 (hCE) 暴露于毒素.
主要成果:
- CDI小鼠在PPAR信号传递,胆固醇和葡萄糖代谢中的基因表达减少.
- 在CDI小鼠中观察到IL-17炎症基因的表达增加.
- 暴露于毒素的细胞培养物表现出PPAR调节,胆固醇代谢和胆酸 (BA) 途径基因的改变表达.
结论:
- 困难菌感染及其毒素显著改变宿主基因表达.
- 宿主胆固醇代谢和胆酸运输/合成途径受到影响.
- 这些发现表明CDI,代谢失调和肠道炎症之间存在联系.
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