一个器官在芯片平台模拟药物代谢沿着肠肝轴
Mara Lucchetti1, Kehinde Oluwasegun Aina2, Léa Grandmougin1
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, L-4362, Luxembourg.
Advanced healthcare materials
|March 7, 2024
概括
一个新的肠肝芯片平台模拟了肠道微生物如何影响药物代谢. 它表明大肠杆菌可以激活结肠直肠癌药物.
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.
- 生物技术是生物技术.
背景情况:
- 人类微生物组通过肠肝轴影响药物代谢,影响药物反应和毒性.
- 由于肠道环境的复杂性,了解这些微生物驱动的效应是具有挑战性的.
- 现有的模型往往无法捕捉到复杂的肠-肝-微生物群相互作用.
研究的目的:
- 开发和验证一个整合肠道和肝脏模型的多器官在芯片 (MOoC) 平台.
- 为了研究微生物代谢在药物处理中的作用,沿着肠-肝轴.
- 评估平台在研究药物代谢和与肠道微生物群相关的毒性方面的实用性.
主要方法:
- 人类微生物交叉体 (HuMiX) 肠上芯片 (GoC) 与Dynamic42肝上芯片 (LoC) 的集成,以创建MOoC.
- 在MOoC中培养肠道和肝脏细胞以确保生命力和功能.
- 使用结肠直肠癌药物诺坦 (irinotecan) 进行概念验证研究,以模拟其代谢.
- 使用液体染色学与双重质谱学 (LC-MS/MS) 结合对伊利诺特干代谢物的分析.
主要成果:
- MOoC平台成功支持了肠道和肝脏细胞的活力和功能.
- 该平台准确地代表了沿肠-肝轴的义诺他干代谢.
- 肠道细菌大肠杆菌 (Escherichia coli) 已被证明可以将静止剂的非活性代谢物 (SN-38G) 代谢成其有毒的形式 (SN-38).
结论:
- 开发的MOoC平台为研究肠道微生物组与药物相互作用提供了一个强大的体外模型.
- 这个平台为药物开发和个性化医疗提供了一种有价值的替代动物模型.
- 它可以研究特定的肠道细菌如何影响药物的疗效和毒性.
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