微生物群调节的代谢物通过调节NLRP6炎症体信号来塑造肠道的微环境
Maayan Levy1, Christoph A Thaiss1, David Zeevi2
1Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell
|December 7, 2015
概括
通过调节NLRP6炎症和抗菌 (AMP) 来调节肠道免疫力. 恢复这种平衡可以治疗疾病和结肠炎.
科学领域:
- 微生物学
- 免疫学
- 胃肠病学
背景情况:
- 宿主微生物组的共同进化对于肠道平衡和疾病至关重要.
- 肠道微环境的调节原理,特别是炎症体的参与,尚未完全理解.
- 调节炎症体活性和肠道免疫力的特定微生物代谢物是未知的.
研究的目的:
- 识别调节宿主微生物组接口的微生物代谢物.
- 阐明这些代谢物影响炎症体信号和抗菌 (AMP) 形状的机制.
- 研究该轴在维持肠道微生物群体稳定性及其治疗潜力的作用.
主要方法:
- 研究了微生物代谢物 (牛素,胰岛素,精子素) 在NLRP6炎症信号调节中的作用.
- 评估了炎症酶对上皮细胞IL-18分泌和下游抗菌 (AMP) 概况的影响.
- 利用便微生物种移植模型研究肠炎的发展和治疗干预措施.
主要成果:
- 鉴定出与微生物相关的代谢物 (氨酸,组胺,精氨酸) 是NLRP6炎症和上皮IL-18分泌的关键调节剂.
- 炎症酶缺乏导致AMP的扭曲,从而促进了失能.
- 大肠炎诱导的微生物通过代谢物抑制了炎症体活动,改变了AMP平衡,有利于其殖民.
- 恢复代谢物-炎症酶-AMP轴改善了结肠炎并使肠道微生物群正常化.
结论:
- 微生物代谢物通过天生的免疫调节在形成宿主微生物群界面方面发挥着关键作用.
- 已识别的代谢物-炎症酶-AMP轴对于维持微生物群体稳定性至关重要.
- 有针对性的代谢干预 (后生物药物) 显示出治疗或预防与失调相关的疾病的前景.
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