没有抗生素预先调整的Cecal微生物组移植标准化了小鼠微生物组
Rye Howard-Stone1, Philip Gerwin2, Darien Capunitan2
1School of Computing, University of Connecticut, Storrs, CT, United States.
Frontiers in microbiology
|August 27, 2025
概括
通过Cecal微生物移植 (CMT) 控制小鼠的肠道微生物组可以改善药物开发. 没有抗生素的CMT建立了稳定的野生型细菌群体,提高了非临床研究的复制性和降低了成本.
科学领域:
- 微生物学
- 药理学
- 翻译医学
背景情况:
- 在小鼠中不受控制的肠道微生物组变异混了非临床发现,影响了免疫成熟,药物代谢和转化到临床环境.
- 微生物组组成与药物反应翻译的失败有关,这突显了对标准化动物模型的需求.
- 由于可变动物模型的复制性不佳和高成本,制药开发面临挑战.
研究的目的:
- 在实验室小鼠中使用Cecal Microbiome Transplant (CMT) 建立具有良好特征,稳定的细菌群体的稳定性和有效性.
- 将CMT与没有抗生素预先调节进行比较.
- 在非临床研究中确定创建可再生肠道微生物组的最佳方法.
主要方法:
- 在具有不同初始肠道细菌特征的异种小鼠群体中进行了Cecal微生物移植 (CMT).
- 用先前的抗生素治疗和不使用的方法来建立稳定的细菌群体.
- 基于AMPLICON序列变异 (ASV) 的测序用于高分辨率的细菌特征监测.
主要成果:
- 一次CMT治疗有效地将小鼠群聚到一个稳定的,与野生类型类似的细菌遗传环境中.
- 与物种级别分析相比,基于ASV的监测提供了更高的分辨率来跟踪细菌差异.
- 抗生素预制降低了CMT菌株吸收的效率,并引入了微生物组合的不受控制的变异.
结论:
- 没有抗生素预制的CMT可以增强对小鼠宿主微生物组成的控制.
- 这种方法提高了非临床药物毒性和疗效研究的有用性,准确性和相关性.
- 通过CMT对小鼠微生物群进行标准化,可以在药物开发中获得更多可转化发现和节省成本.
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