肠上皮层Axin1缺乏通过改变肠道微生物群来保护大肠炎
Shari Garrett1,2, Yongguo Zhang1, Yinglin Xia1
1Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
肠道Axin1的损失通过改变肠道微生物群来保护大肠炎,特别是丰富了Akkermansia muciniphila. 这一发现揭示了Axin1在维持肠道平衡和宿主微生物相互作用方面的新作用.
科学领域:
- 胃肠道学和免疫学
- 微生物组研究 微生物组研究
- 分子生物学分子生物学
背景情况:
- 肠道平衡依赖于宿主细胞和肠道微生物群.
- Wnt/β-catenin信号传递对肠道健康至关重要;其失调与炎症和癌症有关.
- Axin1负面调节Wnt信号传输,但其在宿主微生物相互作用中的作用尚不清楚.
研究的目的:
- 研究肠道Axin1在维持肠道平衡和宿主对炎症的反应中的作用.
- 阐明Axin1影响宿主微生物相互作用和结肠炎的机制.
主要方法:
- 在人类炎症性肠病 (IBD) 数据集中分析了Axin1表达.
- 在肠道上皮细胞 (IECs) 和帕内斯细胞 (PCs) 中产生有条件Axin1淘汰的小鼠模型.
- 利用硫酸 (DSS) 诱导的大肠炎模型,共同住房实验和抗生素治疗.
主要成果:
- 在人类IBD患者的结肠表皮中观察到Axin1表达的增加.
- 缺乏Axin1的小鼠 (ΔIEC, ΔPC) 呈现出改变的杯状细胞分布,帕内斯细胞形态,减少的酶,以及丰富的Akkermansia muciniphila.
- 肠道Axin1的丧失提供了对DSS诱导的大肠炎的保护.
- 与对照小鼠共住增加了Axin1缺乏小鼠的结肠炎易感性.
- 阿克尔曼西亚菌 (Akkermansia muciniphila) 治疗可以减少结肠炎的严重程度.
结论:
- 肠道Axin1在调节肠道平衡和宿主对炎症反应方面发挥着至关重要的作用.
- 肠道Axin1的损失可以防止大肠炎,由表皮Axin1和Akkermansia muciniphila介导.
- Axin1是肠道微生物群和宿主炎症反应的新型调节者,为IBD提供了潜在的治疗点.
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