Light-Sensitive Lactococcus lactis for Microbe-Gut-Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System.
Light-Sensitive Lactococcus lactis for Microbe-Gut-Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System.
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DOI：
10.1021/acsnano.1c11536
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发表时间：
2022-04
期刊：
影响因子：
17.1
通讯作者：
Huizhuo Pan;T. Sun;Meihui Cui;Ning Ma;Chun Yang;Jing Liu;Gaoju Pang;Baona Liu;Lianyue Li-Lianyue
中科院分区：
文献类型：
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作者：
Huizhuo Pan;T. Sun;Meihui Cui;Ning Ma;Chun Yang;Jing Liu;Gaoju Pang;Baona Liu;Lianyue Li-Lianyue
肠-脑轴的发现证明了大脑功能可以受到肠道微生物群代谢产物的影响，因此有很大的机会探索新的工具来调节肠道微生物群，从而影响大脑功能。同时，工程菌作为口服活菌制剂调节宿主的健康稳态，在微生物治疗中受到广泛关注。然而，这种策略是否能够在体内远程调节宿主的脑功能还没有研究。在这里，我们设计了三种蓝光响应益生菌作为口服活生物制剂。它们通过上转换光遗传学微纳系统时空递送和控制。这种微纳系统促进了外源性L.肠内的乳酸，实现了对大脑功能的精确操纵，包括焦虑行为，帕金森病和迷走神经传入。非侵入性和实时益生菌干预策略使从肠道到宿主的通信更加可控，这将使工程微生物能够准确有效地调节宿主的健康。
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 in vivo 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 L. lactis 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.