对酸盐敏感的基因工程益生菌局部释放TNF-α纳米体,对抗炎症性肠病
Bochuan Yuan1, Zhangyu Li2, Yuanyuan Song3
1Beijing Institute of Radiation Medicine, Beijing 100850, China; State Key Laboratory of National Security Specially Needed Medicines, Beijing 100850, China.
概括
工程化益生菌可以储存和释放治疗分子,以响应疾病信号. 这种新的方法通过减少炎症和恢复肠道屏障,有效治疗性结肠炎.
科学领域:
- 微生物学 微生物学
- 胃肠病学 胃肠病学
- 生物技术是生物技术.
背景情况:
- 基因工程益生菌通过分子释放提供临床潜力.
- 细菌有效载荷释放模式对治疗疗效的影响在很大程度上是未知的.
- 炎症性肠病 (IBD) 是研究新型益生菌释放系统的一个模型.
研究的目的:
- 在基因工程益生菌中研究一种新的"产品-商店-发布"模式.
- 开发对酸盐有反应性的工程益生菌来治疗IBD.
- 为了比较两个不同的释放系统 (Hly和 lysis) 在工程 *E. coli Nissle 1917* 中的有效性.
主要方法:
- 经过工程 *Escherichia coli Nissle 1917* (EcN) 来表达TNF-α纳米体 (NbTNF-α).
- 集成的酸盐响应的NarX/L传感和Hly分泌或φX174E溶解系统.
- 通过口服给大肠炎模型注射工程 EcN 菌株 (E5 和 E7).
- 评估了抗炎活性,粘膜屏障恢复,以及体内NbTNF-α水平.
主要成果:
- 在工程E. coli*中确认了NbTNF-α的表达和强烈的抗炎活性.
- 在Hly分泌 (E5) 和 lysis-release (E7) 系统中,在体外释放动力学上表现出类似的.
- 实现了大肠炎的显著减少,其特征是炎症减弱和肠道屏障功能恢复.
- 对于E5和E7菌株,在肠道中观察到可比的NbTNF-α水平.
结论:
- 对工程益生菌的新"产品-商店-释放"策略对炎症性肠道疾病有效.
- 对酸盐有反应的释放系统可以在针对性治疗的工程益生菌中成功实施.
- 这项工作为开发适应疾病的基因工程益生菌提供了新的设计原则.
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