重塑益生菌可通过口服给药有效治疗2型糖尿病
Haihua Ji1, Yiqun Wan2, Shengjie Li3
1State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, 330047, China.
Biomaterials
|November 22, 2024
概括
工程造型的乳球菌乳糖益生菌,屏蔽和武装用于口服,显著改善了小鼠的生存率,并通过增强肠道健康和肝功能来治疗2型糖尿病.
科学领域:
- 生物技术是生物技术.
- 微生物学 微生物学
- 代谢疾病 代谢疾病
背景情况:
- 由于发病率不断上升,2型糖尿病 (T2D) 需要有效,易于获得的治疗方法.
- 目前的T2D疗法往往缺乏用户友好性,生活方式兼容性或经济可行性.
研究的目的:
- 开发一种新的口服益生菌治疗T2D.
- 通过生物对等修改,设计乳球菌以分泌类似葡萄糖素的-1 (GLP-1),并提高其稳定性和有效性.
主要方法:
- 基因工程 Lactococcus lactis 产生 L. lactis-GLP-1 的基因工程.
- 用多巴胺 (DA) 基的"抓手"和β-葡萄糖 (GN) 基的"盾牌" (L. lactis-GLP-1-DA@GN) 进行生物对等武装.
- 在T2D小鼠模型中,口服L. lactis-GLP-1-DA@GN.
主要成果:
- 通过防止胃肠道疾病,GN盾显著增加了生存率 (20666x).
- 在GN代谢释放SCFA后,DA抓手促进了肠道殖民,从而产生了协同治疗效应.
- 口服L. lactis-GLP-1-DA@GN通过改善葡萄糖/脂质平衡,修复器官损伤和调节肠道微生物群,有效治疗T2D.
- 多omics分析表明干预肝脂代谢和氧化调节通路.
结论:
- 使用化学和生物工具组合的重建益生菌为疾病治疗提供了新的策略.
- L. lactis-GLP-1-DA@GN证明了有效和兼容的T2D管理的有希望的方法.
- 这项工作扩大了操纵益生菌用于治疗应用的潜力.
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