新生儿肠道感染通过模式识别受体和改变的神经免疫信号破坏了微生物群-肠-大脑轴
bioRxiv : the preprint server for biology
|February 6, 2026
概括
早期的肠道感染会长期影响微生物群-肠道-大脑轴. 肠表皮NOD1信号传递对免疫反应,屏障修复和预防持久的肠-大脑功能障碍至关重要,益生菌木显示出治疗潜力.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
背景情况:
- 早期的肠道感染可能会破坏微生物群-肠-大脑 (MGB) 轴,导致持续的健康问题.
- 特定宿主信号通路,如NOD1在调解这些长期影响中的作用仍然不完全理解.
研究的目的:
- 研究肠上皮细胞 (IEC) NOD1信号在协调粘膜免疫,屏障修复和早期感染后的神经免疫结果中的作用.
- 确定IEC NOD1信号是否影响长期MGB轴重塑和相关的认知缺陷.
- 探索NOD2配体在缓解感染引起的炎症方面的治疗潜力.
主要方法:
- 在野生型 (WT) 和Nod1缺陷IEC (Nod1ΔIEC) 的小鼠中使用了新生儿肠病原性大肠杆菌 (EPEC) 感染模型.
- 评估了感染后的叶炎症,屏障完整性,上皮细胞增殖和免疫细胞透.
- 在成年期评估了长期的MGB轴效应,包括肠道透性,海马炎症,神经发生和识别记忆.
- 研究了来自益生菌Lactobacillus物种的muropeptides对EPEC诱导的炎症的免疫调节作用.
主要成果:
- 在WT小鼠中,新生儿EPEC感染引起了阴茎炎症,屏障缺陷和降低了上皮细胞增殖,这些在Nod1ΔIEC小鼠中减弱了.
- 在成年WT小鼠中,新生儿感染导致了持续的肠透性,持续的炎症,海马炎症,神经发生变化和识别记忆障碍,在Nod1ΔIEC小鼠中基本上缺席.
- 微生物衍生的NOD2 (muropeptides) 来自乳杆菌减弱的EPEC诱导的粘膜炎症和化学激素诱导,而不会影响细菌负载.
结论:
- IEC NOD1信号是MGB轴在生命早期肠道感染后长期重塑的关键决定因素.
- 破坏IEC NOD1信号传输可以防止持续的肠脑功能障碍和相关的认知缺陷.
- 益生菌衍生型木是一种潜在的治疗策略,用于调节宿主导的免疫反应对肠道感染.
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