体内
炎症性肠病
分泌物
伤口愈合
势垒函数
结肠炎
肠粘膜
肠上皮
微生物学
体外
上皮
生物
细胞生物学
免疫学
医学
疾病
病理
生物化学
生物技术
内科学
作者
Pichet Praveschotinunt,Anna Duraj‐Thatte,Ilia Gelfat,Franziska Bahl,David B. Chou,Neel Joshi
标识
DOI:10.1038/s41467-019-13336-6
摘要
Abstract Mucosal healing plays a critical role in combatting the effects of inflammatory bowel disease, fistulae and ulcers. While most treatments for such diseases focus on systemically delivered anti-inflammatory drugs, often leading to detrimental side effects, mucosal healing agents that target the gut epithelium are underexplored. We genetically engineer Escherichia coli Nissle 1917 (EcN) to create fibrous matrices that promote gut epithelial integrity in situ. These matrices consist of curli nanofibers displaying trefoil factors (TFFs), known to promote intestinal barrier function and epithelial restitution. We confirm that engineered EcN can secrete the curli-fused TFFs in vitro and in vivo, and is non-pathogenic. We observe enhanced protective effects of engineered EcN against dextran sodium sulfate-induced colitis in mice, associated with mucosal healing and immunomodulation. This work lays a foundation for the development of a platform in which the in situ production of therapeutic protein matrices from beneficial bacteria can be exploited.
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