来自早产婴儿的微生物群,这些婴儿患有死角性肠球炎,在人性化的小鼠模型中驱动神经发育障碍
Jing Lu1, Alexander Drobyshevsky2, Lei Lu1
1Department of Pediatrics, Division of Biological Sciences, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.
Microorganisms
|June 15, 2023
概括
在死角性肠球炎 (NEC) 发作之前,婴儿的肠道微生物组会对大脑发育和神经结果产生负面影响. 这表明早期的微生物组是改善早产婴儿长期神经发育障碍的目标.
科学领域:
- 微生物学 微生物学
- 神经科学是一个神经科学.
- 胃肠病学 胃肠病学
背景情况:
- 结核性肠球炎 (NEC) 是导致早产婴儿胃肠道问题和神经发育障碍 (NDI) 的主要原因之一.
- 异常的肠道细菌殖民涉及NEC病原体,并对神经发育产生负面影响.
- 测试了前NEC微生物群落驱动NDI的假设.
研究的目的:
- 调查肠道微生物群落在NEC之前对后代大脑发育和神经结果的影响.
- 为了比较早产婴儿的微生物群的影响,这些早产婴儿发展了NEC (MNEC) 与健康的婴儿 (MTERM).
主要方法:
- 使用了一个人性化的gnotobiotic小鼠模型,怀孕的无菌小鼠与人类婴儿微生物样本进行了测量.
- 对后代小鼠进行了评估,以检测皮质炎症,屏障完整性,行为,大脑成熟 (MRI) 和大脑代谢概况.
主要成果:
- 在MNEC小鼠中,乳房内奥克卢丁和ZO-1的表达减少,炎症增加,肠道屏障功能受损.
- 在MNEC小鼠中,运动能力降低,焦虑增加,情境记忆受损.
- 在MNEC小鼠中,MRI显示大脑成熟延迟,髓化减少,白质组织改变.
- 代谢分析表明,在MNEC小鼠中,大脑中的肉,胆和胆酸类似物发生了显著的改变.
结论:
- 在NEC发作之前的微生物群组成显著影响肠道屏障完整性,大脑发育和神经功能.
- 这些发现突出了肠道微生物群作为缓解早产婴儿NDI的潜在治疗点.
- 这项研究表明,早期肠道微生物组与长期神经发育结果之间存在因果关系.
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