基于“合成生物学-纳米光遗传学”肠菌移植凝胶系统的帕金森症肠脑轴调控研究

肠菌移植用于疾病防治，具有重大理论和现实意义。然而，传统粪菌移植技术，存在生物安全、移植位置、代谢产物均不可控的致命缺陷，导致其机理不清、实施困难、副作用大，严重限制菌群移植应用。针对上述缺陷，本项目拟将合成生物学、上转换光遗传学与纳米生物学相结合，设计构建具有安全高效、准确定植、无创调控功能的纳米水凝胶系统，有效提高肠菌移植可控性，具体包括：1）生物安全更可控：采用乳酸菌，彻底避免病菌混入，使安全更可控；2）移植位置更可控：靶向缓释水凝胶，精准递送菌群，使位置更可控；3）代谢产物更可控：合成生物学-上转换光遗传学调控，使代谢更可控。项目以难治性帕金森症为例，通过体内外实验，对该系统的移植代谢可控性及脑疾病防治效应进行检验。综上，项目将在“菌群移植—疾病防治”领域独辟蹊径，有望突破其应用困局，有效拓展其应用途径，最终为肠菌移植用于疾病防治，提供新思路、新方法和新技术。

Transplantation of gut microbiota for disease prevention has great theoretical and practical significance. However, traditional fecal microbiota transplantation technology has fatal defects in biosafety, transplant position and controlled metabolites. These disadvantages lead to problems such as unclear mechanism, difficult implementation, and serious side effects, which severely restrict the application. In view of the above defects, this project intends to combine synthetic biology, upconversion optogenetics and nanobiology, to design and construct a nano-hydrogel system with safety, efficiency, exact colonization ability, and non-invasive regulation functions. This system can availably improve the maneuverability of the colonized gut microbiota's metabolism, including: 1) Biosafety is more controllable: use lactic acid bacteria to completely avoid the incorporation of extra bacteria, making safety more controllable; 2) Transplantation position is more controllable: targeted and slow-released hydrogel precisely delivers bacteria to gut, making the position more controllable; 3) Metabolites are more controllable: synthetic biology - upconversion optogenetic regulation, making metabolism more controllable. The project takes refractory Parkinson's disease as an example to test the controllability of transplanted metabolism and the prevention of brain diseases through in vitro and in vivo experiments. In all, the project will be unique in the “gut microbiota transplantation - disease prevention” field, and it is expected to break through its dilemma, effectively expand its application, and finally provides new ideas, methods and technologies in gut microbiota transplantation for disease prevention and treatment.