文献类型：期刊文献

英文题名：Biomarker-responsive engineered probiotic diagnoses, records, and ameliorates inflammatory bowel disease in mice

作者：Zou, Zhen -Ping[1];Du, Yue[1];Fang, Ting -Ting[1];Zhou, Ying[1];Ye, Bang -Ce[2]

机构：[1]East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Zhejiang Univ Technol, Inst Engn Biol & Hlth, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gre, Hangzhou 310014, Zhejiang, Peoples R China

年份：2023

卷号：31

期号：2

起止页码：199

外文期刊名：CELL HOST & MICROBE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001012766200001)】；

基金：This work was sponsored by the National Natural Science Foundation of China (22134003) and the National Key Research and Development Program of China (2020YFA0908800). We thank Yong Liang (Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences) for his suggestions regarding the construction of the DSS-induced mouse colitis model.

语种：英文

摘要：Rapid advances in synthetic biology have fueled interest in engineered microorganisms that can diagnose and treat disease. However, designing bacteria that detect dynamic disease-associated biomarkers that then drive treatment remains difficult. Here, we have developed an engineered probiotic that noninvasively monitors and records inflammatory bowel disease (IBD) occurrence and progression in real time and can release treatments via a self-tunable mechanism in response to these biomarkers. These intelligent respon-sive bacteria for diagnosis and therapy (i-ROBOT) consists of E. coli Nissle 1917 that responds to levels of the inflammatory marker thiosulfate by activating a base-editing system to generate a heritable genomic DNA sequence as well as producing a colorimetric signal. Fluctuations in thiosulfate also drive the tunable release of the immunomodulator AvCystatin. Orally administering i-ROBOT to mice with colitis generated molecular recording signals in processed fecal and colon samples and effectively ameliorated disease. i-ROBOT provides a promising paradigm for gastrointestinal and other metabolic disorders.