表观遗传编程调解了异常的肠道微生物群和在产前暴露于德克萨米他的后代中对疾病的易感性
Xiaoqian Lu1, Beidi Chen2, Dan Xu3
1Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Cell reports. Medicine
|February 1, 2024
概括
产前甲暴露 (PDE) 会改变婴儿肠道微生物群的组成,特别是在女性中,增加疾病易感性. 这种子宫内暴露会长期影响肠道发育和胆酸代谢.
科学领域:
- 微生物学 微生物学
- 发展生物学 发展生物学
- 胃肠病学 胃肠病学
背景情况:
- 产前甲暴露 (PDE) 与成人疾病易感性有关.
- 对于PDE对婴儿肠道微生物群和疾病联系的影响尚不清楚.
研究的目的:
- 调查产前德克萨米他松疗法 (PDT) 对婴儿肠道微生物群组成的影响.
- 探索PDE对肠道微生物群和后代疾病易感性的长期影响.
主要方法:
- 对婴儿和后代大鼠肠道微生物群组成的分析.
- 评估胆酸代谢和肝损伤.
- 对Muc2和CDX2表达的研究.
- 在体外和体内实验中对甲的分子机制进行实验.
主要成果:
- 在婴儿中,PDE诱导了性别差异的肠道微生物群变化,在女性中持续存在.
- 暴露于PDE的雌性后代大鼠表现出改变的肠道微生物群和增加胆固醇性肝损伤的易感性.
- 通过GR/HDAC11信号传递和CDX2表观遗传修饰,PDE抑制了Muc2的表达,导致肠道失调.
结论:
- 产后发育症会导致子宫内肠道发育不良,导致肠道微生物群异常,并增加后代对疾病的易感性.
- PDE对肠道微生物群和新陈代谢的性别特异性影响显著.
- 了解这些机制可以为减轻PDE诱导的健康风险制定策略.
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