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肠道转基因输送与本地大肠杆菌底盘允许持续的生理变化

Baylee J Russell1, Steven D Brown1, Nicole Siguenza1

  • 1Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.

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概括
此摘要是机器生成的。

工程化本地细菌可以殖民肠道, 提供持久的治疗效益. 这种方法使活细菌疗法 (LBT) 能够通过直接向宿主微生物组提供特定功能来逆转疾病.

关键词:
胆酸新陈代谢复杂的肠道微生物组葡萄糖平衡肠道微生物组代谢过程微生物与宿主之间的相互作用非模型肠道微生物精确微生物组调制合成生物学二型糖尿病

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科学领域:

  • 微生物组研究
  • 细菌治疗药物
  • 主体与微生物的相互作用

背景情况:

  • 活体细菌疗法 (LBT) 的目的是通过植入有益的微生物来恢复肠道健康.
  • 工程微生物往往无法在常规培养 (CR) 主体中的具有挑战性的肠道环境中殖民.
  • 开发有效的LBT需要克服宿主肠道中的殖民障碍.

研究的目的:

  • 研究将本地细菌作为治疗功能提供给肠道微生物的基架.
  • 证明工程原生大肠杆菌在CR宿主中持续植入和功能影响的可行性.
  • 建立使用本地细菌底盘的治疗意图的LBT概念证明.

主要方法:

  • 从传统养 (CR) 鼠中分离和修改本地大肠杆菌菌株.
  • 设计这些本地大肠杆菌菌株以表达特定的功能基因用于治疗目的.
  • 将工程原生大肠杆菌注入CR宿主以评估移植和生理效应.

主要成果:

  • 工程化本地大肠杆菌菌株在宿主肠道中实现了永久植入.
  • 重新引入改良原生细菌导致CR宿主生理的持久功能变化.
  • 这些工程原生细菌在施用几个月后在CR宿主中逆转了病理.

结论:

  • 本地细菌作为转基因传递的有效底盘,克服了CR宿主中的殖民挑战.
  • 这一策略使得能够诱导持续有益功能的活细菌疗法 (LBT) 的开发成为可能.
  • 这种方法促进了对微生物功能的机制研究,并为具有治愈潜力的LBT提供了途径.