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克服与便微生物群移植相关的捐赠者变异性和风险,通过菌体介导的治疗方法

Torben Sølbeck Rasmussen¹, Xiaotian Mao², Sarah Forster²

¹Section of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark. torben@food.ku.dk.

|July 2, 2024

概括

修改的便病毒移植 (FVT) 通过提高安全性和有效性,对治疗C. difficile感染有希望. 溶剂洗剂处理和菌体传播为克服当前FMT和FVT方法的挑战提供了有希望的策略.

科学领域:

微生物学微生物学
病毒学病毒学
胃肠病学胃肠病学

背景情况:

便微生物群移植 (FMT) 和便病毒组移植 (FVT) 对于复发的Clostridioides difficile感染是有效的,可能是通过菌体调节.
挑战包括捐赠者的变异性,查成本和病原体转移风险 (例如,真核病毒) 与FMT/FVT,限制更广泛的应用.

研究的目的:

为更广泛的临床应用开发增强的FVT方法,解决安全性和有效性问题.
在Clostridioides difficile感染小鼠模型中评估加工的FVT疗效.

主要方法:

开发了三种FVT处理方法:用于细菌体和真核生物病毒去除的化学定位传播 (FVT-ChP),用于包裹病毒无活化的溶剂洗剂处理 (FVT-SDT) 和用于RNA病毒抑制的pyronin-Y处理 (FVT-PyT).
评估了对小鼠C. difficile感染的疗效,比较了FVT-SDT,FVT-ChP,FVT-PyT,未经处理的FVT (FVT-UnT),FMT和盐水.

主要成果:

与FMT,FVT-PyT和盐水相比,FVT-SDT,FVT-UnT和FVT-ChP显著降低了C. difficile殖民和毒素水平.
在7/8小鼠中,FVT-SDT证明了潜在的C. difficile消除,具有qPCR阴性.
微生物组,细胞因子配置和组织学的变化支持了治疗疗效,而菌体转移被确定为关键因素.

结论:

修改后的FVT策略在克服与FMT/FVT相关的供体变异性和感染风险方面显示出有希望.
用溶剂清洁剂处理和捐赠菌体的化学定位传播是有效治疗C. difficile的有希望的方法.

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