Establishing remote communication between human operator and engineered intestinal microbe via bio-electronic optical language
Establishing remote communication between human operator and engineered intestinal microbe via bio-electronic optical language
ABSTRACT Synthetic biology enables microbes to be engineered to detect biomarkers and deliver therapies in situ, offering advantages such as self-replication and localized response and treatment. However, the engineered microbes in the intestine remains a “black box”, the status of microbial functionality is inaccessible, and the activation of microbial functions is uncontrollable. There is a demand of a “language” between microbes and human for real-time and in-situ monitoring and controlling engineered microbes in the intestine. Light, due to its advantages of specificity and accuracy in the body, was chosen as the language to establish an interactive communication path between human and the microbes with the features of sophisticated monitoring and controlling. For effectively remote operation of this “language” in the intestine, we introduced an electronic capsule as the intermedia, translating information and instructions understandable for human operator into bacterial regulatory and detectable signals in vivo. In this paper, the electronic capsule and the engineered Escherichia coli Nissle 1917 (EcN) strains were designed in a collaborative manner. An EcN-to-capsule bioluminescent signal transmission was established and testified as the language to report the status of engineered EcN, especially the response of EcN to intestinal environment. Similarly, another capsule-to-EcN optogenetic signal transmission was established and testified as the language to control the function of engineered EcN, especially the secretion of therapeutic substances. On this basis, bidirectional communication between human operator and intestinal microbes was achieved via bidirectional bio-electronic optical language. The communication was established to monitor and regulate engineered EcN community in the intestine in 50-90 kg live pigs. The in vitro and in vivo estimations demonstrated the capabilities of monitoring and regulating the engineered microbes, offering a remotely controllable language-based communication between human operator and internal intestinal microbes.
Du Taofeng、Wang Hanxin、Xue Huimin、Liu Xinyu、Li Mingshan、Li Lianyue、Yang Chao、Dai Pengxiu、Sun Dawei、Lu Shenjunjie、Wang Yaxin、Shi Yanyan、Wang Hanjie、Feng Zhijie、Yang Haoyan、Li Hongxiang、Cui Meihui、Zhang Xinyu、Liu Jing、Liu Duo、Ma Xiaoyan
The College of Veterinary Medicine, Northwest Agriculture and Forestry UniversityThe College of Veterinary Medicine, Northwest Agriculture and Forestry UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversityKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of TechnologyThe College of Veterinary Medicine, Northwest Agriculture and Forestry UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversityResearch Center of Clinical Epidemiology, Peking University Third HospitalSchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversityThe College of Veterinary Medicine, Northwest Agriculture and Forestry UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin UniversitySchool of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin University||Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Frontiers Research Institute for Synthetic Biology, Tianjin UniversityKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology
生物工程学生物科学现状、生物科学发展通信
Du Taofeng,Wang Hanxin,Xue Huimin,Liu Xinyu,Li Mingshan,Li Lianyue,Yang Chao,Dai Pengxiu,Sun Dawei,Lu Shenjunjie,Wang Yaxin,Shi Yanyan,Wang Hanjie,Feng Zhijie,Yang Haoyan,Li Hongxiang,Cui Meihui,Zhang Xinyu,Liu Jing,Liu Duo,Ma Xiaoyan.Establishing remote communication between human operator and engineered intestinal microbe via bio-electronic optical language[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2024.05.24.595785.点此复制
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