臭菌splanchnicus通过GDP-L-糖分泌来挽救与衰老相关的肠道P-糖蛋白损伤
Cheng Cui1,2, Lu Fang3,4,5, Lei Li4,6,7
1Drug Clinical Trial Center, Department of Pharmacy, Peking University Third Hospital, Beijing, China.
Nature communications
|November 27, 2025
概括
肠道细菌不平衡导致与年龄相关的肠道P-糖蛋白 (P-gp) 功能下降. 恢复微生物Odoribacter splanchnicus或其代谢物GDP-L-fucose可以改善老年人的药物吸收.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 胃肠病学 胃肠病学
背景情况:
- 肠道P-糖蛋白 (P-gp/ABCB1) 限制了药物吸收,但其与年龄相关的下降不清楚.
- 肠道微生物群随着年龄的增长而发生变化,可能会影响P-gp功能和异生物代谢.
研究的目的:
- 调查肠道微生物群失生症在与年龄相关的P-gp缺乏症中的作用.
- 为了确定特定的微生物物种和代谢物参与维护肠道P-gp功能.
主要方法:
- 对人类队列和小鼠模型的综合多学科分析.
- 确定关键的微生物物种及其代谢途径.
- 研究将微生物代谢物与P-gp表达和功能联系起来的分子机制.
主要成果:
- 肠道微生物群失调有助于与年龄相关的P-gp缺乏.
- 消耗的 Odoribacter splanchnicus 损害了肠道的 P-gp 功能.
- O. splanchnicus产生GDP-L-糖,通过促进eIF4E酸化和c-Jun驱动的ABCB1表达,恢复P-gp功能.
结论:
- 一个微生物群-代谢物-载体信号轴维持肠道排毒.
- 向O. splanchnicus或GDP-L-fucose可以防止老年人群的不良药物反应.
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