Construction of an engineered Escherichia coli with enhanced intestinal colonization and anti-inflammatory efficacy in colitis

Abstract

Engineered probiotics are considered as effective and safe therapeutic strategies for the treatment of various diseases. Escherichia coli Nissle 1917 (EcN) has been widely used as a chassis strain for its safety and well-established genetic manipulation system. The limited intestinal colonization ability of EcN hampers its potential as a chassis for constructing synthetic probiotics in therapeutic applications. Here, an engineered EcN strain with high gastric acid and bile salts tolerance as well as enhanced intestinal adhesion ability was constructed by improving the expression of gastric acid and bile salts tolerance-associated genes and strengthening the expression of curli fiber formation genes, respectively. Meanwhile, oral administration of this engineered strain to colitis mice alleviated the disease severity and restored the disordered gut microbiome by decreasing the abundance of Escherichia-Shigella, whereas increasing norank_f_Muribaculaceae. We engineered EcN to improve its probiotic properties and anti-colitis efficacy, thereby establishing a platform for precision-designed synthetic probiotics.