NAD+前体和胆酸封存治疗临床前耐火性环境肠功能障碍
Atika Malique1, Shengxiang Sun1, Kanta Chandwe2
1Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Science translational medicine
|January 3, 2024
概括
儿童的环境肠道功能障碍 (EED) 涉及小肠损伤,影响生长和免疫力. 恢复蛋白质,尼古丁胺胺二核酸 (NAD+) 和减少胆酸可以治疗EED.
科学领域:
- 胃肠病学 胃肠病学
- 儿童营养学 儿童营养学
- 分子生物学分子生物学
背景情况:
- 环境肠道功能障碍 (EED) 是一个影响数百万儿童的全球健康问题,其特点是生长障碍,疫苗反应和营养吸收.
- EED的主要特征包括小肠损伤,关键的先天性免疫细胞 (Paneth和杯细胞) 的丧失,以及改变的胆酸代谢.
- 失调的尼古丁胺胺氨基二核酸 (NAD+) 合成信号涉及到EED的发病因子,与线性生长不良相关.
研究的目的:
- 调查EED的潜在机制,并确定潜在的治疗点.
- 探索低蛋白饮食 (LPD) 在回顾EED特征中的作用及其与NAD+代谢和胆酸的相互作用.
- 评估NAD+前体和胆酸分离剂在改善EED类病理方面的疗效.
主要方法:
- 使用的小鼠模型食同热量低蛋白饮食 (LPD),以模仿EED的组织病理学和转录基因变化.
- 研究了在小鼠的肠表皮中删除Nampt,NAD+救援通路酶的影响.
- 评估了单独或组合补充NAD+前体或胆酸分离剂对LPD诱导缺陷的影响.
主要成果:
- 在小鼠中的LPD消耗复制了EED基因病理学和转录基因改变,独立于微生物群,增加血清和便胆酸.
- 患有耐火性EDD的儿童在NAD+合成酶中表现出单核酸多态性.
- 肠上皮质的Nampt删除加剧了帕内斯细胞功能障碍,而LPD则使其恶化. 补充NAD+前体或胆汁酸序列剂部分恢复了帕内斯细胞缺陷,联合治疗完全恢复了他的病理学.
结论:
- EED的发病包括帕内斯和杯细胞损失,小性缩,胆酸增加和NAD+合成受损.
- 鼠标的LPD回顾了EED的关键特征,强调了营养状况和代谢失调的作用.
- 针对蛋白质补充,NAD+增强和胆酸减少的治疗策略显示出治疗儿童耐火性EDD的前景.
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