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

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	Construction of an engineered Escherichia coli strain with enhanced intestinal colonization and anti-inflammatory efficacy in colitis
	Yu, PJ; Zhou, WJ; Li, CY; Sun, Q; Yang, YP
	2026
发表期刊	Cell. Mol. Immunol.
ISSN	1672-7681
卷号	23 期号:6 页码:635-653
摘要	Engineered probiotics are considered effective and safe therapeutic strategies for the treatment of various diseases. Escherichia coli Nissle 1917 (EcN) has been widely used as a chassis strain because of its safety and well-established genetic manipulation system. However, the limited intestinal colonization ability of EcN limits its potential as a chassis for the construction of synthetic probiotics. Here, an engineered EcN strain (EcN-CPM) with enhanced gastric acid and bile salt tolerance and improved intestinal adhesion was constructed. Oral administration of EcN-CPM to mice with colitis alleviated disease severity and reshaped the disordered gut microbiome by decreasing the abundance of Escherichia-Shigella while increasing the abundance of norank_f_Muribaculaceae. Mechanistically, the EcN-CPM supernatant directly promoted the proliferation of norank_f_Muribaculaceae, a short-chain fatty acid (SCFA)-producing genus. Targeted metabolomics revealed that EcN-CPM restored the DSS-induced depletion of SCFAs, which were negatively correlated with the abundance of Escherichia-Shigella and positively correlated with the abundance of norank_f_Muribaculaceae. Consistent with these findings, EcN-CPM treatment upregulated the expression of Treg-associated markers (Foxp3, Ctla4, and Cd25) and downregulated the expression of Th17-related genes (IL-17A and Roryt) in colonic tissues, restoring the IL-17A/Foxp3 ratio to homeostasis. Untargeted metabolomics further demonstrated that EcN-CPM uniquely restored the levels of seven anti-inflammatory metabolites depleted by DSS treatment. Collectively, these findings demonstrate that EcN-CPM alleviates intestinal inflammation by remodeling the gut microbiota to increase the production of SCFAs and anti-inflammatory metabolites, thereby driving a shift in Th17- and Treg-associated transcriptional signatures. This study establishes a platform for precision-designed synthetic probiotics with enhanced probiotic properties.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/15161
专题	其他
推荐引用方式 GB/T 7714	Yu, PJ,Zhou, WJ,Li, CY,et al. Construction of an engineered Escherichia coli strain with enhanced intestinal colonization and anti-inflammatory efficacy in colitis[J]. Cell. Mol. Immunol.,2026,23(6):635-653.
APA	Yu, PJ,Zhou, WJ,Li, CY,Sun, Q,&Yang, YP.(2026).Construction of an engineered Escherichia coli strain with enhanced intestinal colonization and anti-inflammatory efficacy in colitis.Cell. Mol. Immunol.,23(6),635-653.
MLA	Yu, PJ,et al."Construction of an engineered Escherichia coli strain with enhanced intestinal colonization and anti-inflammatory efficacy in colitis".Cell. Mol. Immunol. 23.6(2026):635-653.

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2026071410.pdf（11509KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文