华东师范大学叶海峰课题组宣布他们研究出葡萄糖反应性益生菌对小鼠和猴子血糖调节的作用。相关论文于2026年8月12日发表于国际顶尖学术期刊《自然》杂志上。

研究组开发了一种工程口服的葡萄糖传感和功能反应益生菌活药，用于基于“感知和反应”的糖尿病血糖控制。小组创建了一个基于合成基因电路的葡萄糖传感器，该电路结合了葡萄糖应答转录调节因子HexR和合成启动子。在口服携带传感器的工程益生菌后，这些细胞暂时驻留在肠道中，并调节治疗性转基因的表达，以应对超过正常阈值的葡萄糖水平。

该研究组展示了工程益生菌在多种糖尿病动物和非人灵长类动物模型中控制血糖的功效，表明长期口服益生菌可以明显改善血脂状况，同时也可以减轻多种糖尿病并发症的发生。他们的基于益生菌的活药能够根据实时血糖水平给药，为代谢治疗提供了一个可编程的、可口服的感知和反应平台，无需移植。

据介绍，以设计细胞为主题的持续和控制的降糖药物递送被认为是糖尿病治疗的有效策略。然而，目前的技术依赖于外部信号控制或已被编程到哺乳动物细胞主题合成基因网络中，这引起了移植的安全问题。

附：英文原文

Title: Glucose-responsive probiotics for glycaemic modulation in mice and monkeys

Author: Guan, Ningzi, Kong, Deqiang, Gao, Xianyun, Niu, Lingxue, Zhou, Yang, Yu, Guiling, Gao, Tian, Liu, Mengyao, Ma, Wenbo, Jin, Yiyu, Yin, Jianli, Zhao, Shangang, Ye, Haifeng

Issue&Volume: 2026-08-12

Abstract: Sustained and controlled delivery of glucose-lowering agents using engineered designer cells is recognized as an effective strategy for diabetes therapy1. However, current technologies rely on external signal control or have been programmed into mammalian cells using synthetic gene networks, which pose safety concerns arising from transplantation2,3. Here we developed an engineered oral-deliverable glucose-sensing and functional response probiotic living drug for ‘sense-and-respond’-based control of diabetic blood glucose. We created a glucose sensor based on a synthetic gene circuit that incorporates the glucose-responsive transcriptional regulator HexR, coupled with a synthetic promoter. Upon oral administration of the engineered probiotics carrying the sensor, the cells reside temporarily in the intestine and regulate the expression of therapeutic transgenes in response to glucose levels that exceed the normal threshold. We show efficacy from the engineered probiotics for glycaemic control in multiple diabetic mouse and non-human primate models, demonstrating that long-term oral administration drives clear improvements in lipid profiles, while also attenuating development of multiple diabetic complications. Our probiotics-based living drug enables therapeutic dosing in response to real-time blood glucose levels, providing a programmable, orally deliverable sense-and-respond platform for metabolic therapy without transplantation.

DOI: 10.1038/s41586-026-10909-6

Source: https://www.nature.com/articles/s41586-026-10909-6