Pan Huizhuo, Sun Tao, Cui Meihui, Ma Ning, Yang Chun, Liu Jing, Pang Gaoju, Liu Baona, Li Lianyue, Zhang Xinyu, Zhang Weiwen, Chang Jin, Wang Hanjie
School of Life Sciences, Tianjin University, Tianjin, 300072, China.
Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin, 300072, China.
ACS Nano. 2022 Apr 26;16(4):6049-6063. doi: 10.1021/acsnano.1c11536. Epub 2022 Apr 1.
The discovery of the gut-brain axis has proven that brain functions can be affected by the gut microbiota's metabolites, so there are significant opportunities to explore new tools to regulate gut microbiota and thus work on the brain functions. Meanwhile, engineered bacteria as oral live biotherapeutic agents to regulate the host's healthy homeostasis have attracted much attention in microbial therapy. However, whether this strategy is able to remotely regulate the host's brain function has not been investigated. Here, we engineered three blue-light-responsive probiotics as oral live biotherapeutic agents. They are spatiotemporally delivered and controlled by the upconversion optogenetic micro-nano system. This micro-nano system promotes the small intestine targeting and production of the exogenous in the intestines, which realizes precise manipulation of brain functions including anxiety behavior, Parkinson's disease, and vagal afferent. The noninvasive and real-time probiotic intervention strategy makes the communiation from the gut to the host more controllable, which will enable the potential for engineered microbes accurately and effectively regulating a host's health.
肠道-脑轴的发现已证明，脑功能会受到肠道微生物群代谢产物的影响，因此探索调节肠道微生物群从而作用于脑功能的新工具存在重大机遇。同时，作为调节宿主健康稳态的口服活生物治疗剂，工程菌在微生物治疗中备受关注。然而，这种策略是否能够远程调节宿主的脑功能尚未得到研究。在此，我们构建了三种蓝光响应益生菌作为口服活生物治疗剂。它们通过上转换光遗传学微纳系统进行时空递送和控制。该微纳系统促进了小肠靶向性以及肠道中外源物质的产生，实现了对包括焦虑行为、帕金森病和迷走神经传入在内的脑功能的精确调控。这种无创且实时的益生菌干预策略使肠道与宿主之间的交流更具可控性，这将使工程微生物准确有效地调节宿主健康成为可能。
