炎症性肠病
生物
生物标志物
疾病
益生菌
结肠炎
肠道菌群
机制(生物学)
溃疡性结肠炎
结直肠癌
计算生物学
细菌
免疫学
生物信息学
癌症
病理
医学
生物化学
遗传学
哲学
认识论
作者
Zhen-Ping Zou,Yue Du,Ting-Ting Fang,Ying Zhou,Bang‐Ce Ye
标识
DOI:10.1016/j.chom.2022.12.004
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 responsive 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.
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