2019/12/06 by Pichet Praveschotinunt, Anna Duraj‐Thatte, Ilia Gelfat +3 · 463 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Nursing · #Barrier function #Biochemistry #Biology #Biotechnology #Cell biology #Clostridium difficile and Clostridium perfringens research #Colitis #Digestive system and related health #Disease #Epithelium #Immunology #In vitro #In vivo #Infant Nutrition and Health #Inflammatory bowel disease #Intestinal epithelium #Intestinal mucosa #Medicine #Microbiology #Pathology #Secretion #Wound healing
paper · pdf · doi:10.1038/s41467-019-13336-6
published in Nature Communications 10(1), 5580 (Nature Portfolio)
openalex publication_date 2019/12/06 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
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.