中国科学院深圳先进技术研究院钟超团队近日取得一项新成果。经过不懈努力，他们的最新研究揭示了工程活胶分泌治疗蛋白治疗炎症性肠病。相关论文于2026年1月19日发表在《自然—生物技术》杂志上。

在这里，课题组设计了一种具有血液诱导基因回路的非致病性大肠杆菌，该基因回路分泌藤条来源的粘附蛋白CP43K和治疗性肠道屏障愈合因子TFF3，以应对胃肠道出血，这是严重炎症性肠病（IBD）的一个指标。黏附蛋白的产生使细菌能在炎症组织中持续驻留，单次直肠给药后粘附时间可达10天，口服给药后可达7天，该效应依赖出血诱导的粘附机制。在两种炎症性肠病小鼠模型（葡聚糖硫酸钠诱导的结肠炎模型和白细胞介素-10敲除小鼠模型）中，该疗法能改善体重恢复、逆转结肠缩短并减少肠道出血。此外，治疗减少肠道炎症，促进粘膜修复，恢复肠道屏障完整性，显示出综合治疗效果。

研究人员表示，工程细菌分泌肠道治疗药物一直受到限制，因为它们对病理线索的自主感知能力差，无法维持局部的、长期的治疗活性。

附：英文原文

Title: Engineered living glues secrete therapeutic proteins for treatment of inflammatory bowel disease

Author: Ge, Changhao, Jiang, Shanshan, Dong, Xiaomin, Jiang, Xiaoyu, Zhi, Weiliang, Yang, Chenhao, Xiang, Yunqing, Chu, Chun, Yang, Peilang, Zhang, Qian, Chen, Xin, Liu, Yan, Huang, Shuqiang, Liu, Yifan, Shi, Xiaoshan, Lin, Jing, An, Bolin, Huang, Peng, Zhong, Chao

Issue&Volume: 2026-01-19

Abstract: Engineering bacteria to secrete gut therapeutics has been limited by their poor autonomous sensing of pathological cues and inability to sustain localized, long-term therapeutic activity. Here we engineer nonpathogenic Escherichia coli with a blood-inducible gene circuit that secretes the barnacle-derived adhesive protein CP43K and the therapeutic gut-barrier-healing factor TFF3 in response to gastrointestinal bleeding, an indicator of severe inflammatory bowel disease (IBD). Adhesive production enables sustained bacterial attachment to inflamed tissues for up to 10days or 7days following a single rectal or oral administration, respectively. This effect depends on bleeding-induced adhesion. Using two mouse models of IBD, the colitis model induced by dextran sulfate sodium and the interleukin-10-knockout mouse model, we demonstrate improved weight recovery, reversed colonic shortening and reduced intestinal bleeding. Additionally, the treatment decreases intestinal inflammation, promotes mucosal repair and restores gut barrier integrity, demonstrating comprehensive therapeutic efficacy.

DOI: 10.1038/s41587-025-02970-9

Source: https://www.nature.com/articles/s41587-025-02970-9