EcNP3

EcNP3 is an engineered live biotherapeutic product (eLBP) developed using the *Escherichia coli* Nissle 1917 (EcN) probiotic strain as a chassis. It is specifically designed to treat inflammatory bowel disease (IBD) by providing sustained restoration of propionate levels in the gastrointestinal tract. The strain was constructed by introducing a propionate biosynthetic pathway (comprising the genes *ldhA*, *pct*, *lcdA*, and *acuI*) and utilizing CRISPR-Cas9 to knock out genes related to acetate synthesis (*pflB* and *poxB*) to optimize propionate production. EcNP3 functions by promoting the polarization of macrophages toward an anti-inflammatory phenotype and increasing the expression of the anti-inflammatory cytokine IL-10. This immunomodulatory effect is mediated through the activation of G protein-coupled receptor 43 (GPR43) and the inhibition of histone deacetylase 1 (HDAC1), which enhances histone acetylation and gene transcription. In preclinical models, EcNP3 has demonstrated the ability to improve intestinal mucosal barrier integrity and reduce inflammatory infiltration.

Other names

engineered propionate-producing probiotic EcNP3engineered Escherichia coli Nissle 1917 P3