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工程化益生菌通过分泌PCSK9纳米体和调节肠道微生物群来改善超脂血症和动脉样硬化

Chuan Wang^1,2,3, Junyue Xing^1,2,4, Huan Zhao⁵

¹National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou China.

Bioengineering & translational medicine

|November 17, 2025

概括

工程益生菌通过口服提供一种新的PCSK9纳米体,以降低胆固醇和降低心血管疾病风险. 这种方法为注射疗法和他类药物提供了成本效益高,方便的替代方案.

科学领域:

生物技术是生物技术.
微生物学微生物学
心血管医学心血管医学

背景情况:

升高的低密度脂蛋白胆固醇 (LDL-C) 是心血管疾病 (CVD) 的主要驱动因素.
蛋白转化酶子素/素9型 (PCSK9) 抑制剂有效降低LDL-C,但价格昂贵,并通过注射给药.
需要更容易获得和更具成本效益的降低LDL-C的策略.

研究的目的:

开发一种能够口服表达和输送PCSK9纳米体 (PCSK9nb) 的工程益生菌.
在临床前模型中评估这种工程益生菌在降低LDL-C,缓解动脉样硬化和改善代谢参数方面的有效性.
将工程益生菌的治疗潜力与阿托瓦斯塔丁等常规治疗方法进行比较.

主要方法:

构建一个表达人类PCSK9纳米体片段的工程益生菌菌株.
在体外和体内评估PCSK9nb的表达,释放,生物相容性和稳定性.
在超脂血症和动脉样硬化的小鼠模型中评估治疗效果,包括肠道微生物群分析和与阿托瓦斯塔丁的比较.

主要成果:

口服工程益生菌导致体内表达和释放PCSK9nb.
血清LDL-C水平,体重和肝脂积累的显著降低.
缓解动脉样硬化,增加肝脏的LDL受体 (LDLR) 表达,并调节肠道微生物群.
治疗疗效与阿托瓦斯塔丁相当,系统性炎症减少.

结论:

工程益生菌代表了口服PCSK9向治疗药物的可行策略.
这种新的方法提供了一个潜在的更实惠和符合当前注射PCSK9抑制剂和他类药物的替代方案.
这项研究为开发超脂血症和心血管疾病治疗提供了新的途径.

关键词:

在PCSK9中动脉样硬化动脉样硬化工程设计的益生菌.过高脂血症是什么意思纳米体是一个纳米体.通过口服传递的口服传递.

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