通过在小鼠胃肠道中通过工程化益生菌酵母提高大分子的肠道吸收
Hitesh P Gelli1, Karl Alex Hedin1, Martin F Laursen2
1Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
Trends in biotechnology
|December 10, 2024
概括
工程酵母产生细胞透 (CPPs) 增强肠道的透性. 这种新的方法改善了治疗性大分子的吸收,提供了一种新的非侵入性药物输送方法.
科学领域:
- 生物技术是生物技术.
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 由于肠道吸收不良,口服类药物递送面临重大挑战.
- 工程微生物为药物输送提供了一个有希望的替代方案,可能提高治疗效率.
- 工程微生物和治疗药物之间的协同相互作用使新的非侵入性治疗策略成为可能.
研究的目的:
- 为了设计益生菌酵母Saccharomyces boulardii以在现场产生细胞透 (CPPs).
- 评估工程酵母菌株提高肠道透性的能力.
- 评估CPP产生的酵母在改善微分子吸收中的安全性和有效性.
主要方法:
- 通过将CPP基因整合到酵母染色体中,工程化Saccharomyces boulardii菌株来表达四种不同的CPP (RRL螺旋,Shuffle,Penetramax,PN159).
- 在实验室中评估肠道透性,使用CACO-2细胞模型与CPP生产酵母菌株.
- 在小鼠体内评估,在10天内给予Sb PN159并测量FITC-dextran转位和炎症迹象.
主要成果:
- 三种基因改造的CPP生产酵母菌株在体外显著增加了肠道透性,但没有引起细胞毒性.
- 在体内研究表明,通过口服注射用于产生PN159 (Sb PN159) 的Saccharomyces boulardii导致小鼠FITC-dextran转位的显著增加.
- 在小鼠接受Sb PN159治疗10天后,没有检测到任何可观察到的炎症.
结论:
- 工程微生物可以用于生产治疗性,如CPPs,直接在胃肠道内.
- 这项研究提供了第一个证据,即工程微生物可以调节宿主肠道的透性,为改善大分子的口服吸收铺平了道路.
- 使用CPPs设计的Saccharomyces boulardii是一种新且潜在的安全的非侵入性策略,用于增强口服药物输送.
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