小柯机器人

美国加州大学圣迭戈分校Amir Zarrinpar小组发现，用自身大肠杆菌底盘进行肠道转基因传递可实现持久的生理变化。2022年8月4日出版的《细胞》杂志发表了这项成果。

研究人员表示，活细菌疗法（LBT）可以通过移植到肠道并在宿主体内提供持续的有益功能来逆转疾病。然而，由于工程微生物（即底盘）难以在宿主的肠道环境中定植，因此在功能上操纵常规饲养（CR）宿主的肠道微生物组一直不成功。

研究人员使用自身细菌作为转基因传递的底盘，来影响CR宿主的生理状况。从CR小鼠的粪便培养物中分离出的自身大肠杆菌被改造成表达功能性基因。这些菌株的重新引入诱导了肠道内的持久吞噬。此外，工程化的自身大肠杆菌可以诱导功能变化，影响CR宿主的生理学，并在给药后数月逆转病理。因此，使用自身细菌作为底盘来"敲入"特定功能，可以对CR宿主微生物组中的特定微生物活动进行机理研究，并实现具有治疗目的的LBT。

附：英文原文

Title: Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes

Author: Baylee J. Russell, Steven D. Brown, Nicole Siguenza, Irene Mai, Anand R. Saran, Amulya Lingaraju, Erica S. Maissy, Ana C. Dantas Machado, Antonio F.M. Pinto, Concepcion Sanchez, Leigh-Ana Rossitto, Yukiko Miyamoto, R. Alexander Richter, Samuel B. Ho, Lars Eckmann, Jeff Hasty, David J. Gonzalez, Alan Saghatelian, Rob Knight, Amir Zarrinpar

Issue&Volume: 2022-08-04

Abstract: Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to “knock in” specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent.

DOI: 10.1016/j.cell.2022.06.050

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00843-1