@article{Wang2026, 
author = {Hao Wang and Jinsong Zhang and Wen Li and Leyi Chu and Xiaofeng Ruan and Meng Zhou and Tianling Pan and Yue Li and Jinzhi Ma and Peng Xiao and Hong Gao},
title = {Engineered probiotic Escherichia coli Nissle 1917 delivery of GPX4 suppresses pyroptosis and protects against sepsis},
year = {2026},
journal = {Food Science and Human Wellness},
keywords = {Escherichia coli Nissle 1917, Engineered probiotic, Sepsis, Pyroptosis, GPX4, Gut-liver axis},
url = {https://www.sciopen.com/article/10.26599/FSHW.2026.9251194},
doi = {10.26599/FSHW.2026.9251194},
abstract = {Sepsis remains a leading cause of mortality worldwide, driven by dysregulated inflammation and organ failure, with limited targeted therapies. Pyroptosis, mediated by gasdermin D (GSDMD), amplifies sepsis pathology through lipid peroxidation-dependent mechanisms, yet direct interventions are scarce. Leveraging the probiotic Escherichia coli Nissle 1917 (EcN) for gut-targeted delivery, we engineered EcN to secrete glutathione peroxidase 4 (GPX4), a pivotal antioxidant enzyme that curbs lipid peroxidation and pyroptosis. In an LPS-induced murine sepsis model, prophylactic oral EcN-GPX4 enhanced survival, mitigated multi-organ damage, and suppressed GSDMD cleavage across tissues. Dual mechanisms included: alleviation of oxidative stress and lipid peroxidation to block pyroptosis; and gut microbiota remodeling, enriching Ligilactobacillus murinus, which correlated with reduced LPS translocation and dampened arachidonic acid–linked pro-inflammatory metabolism. Via the gut–liver axis, EcN-GPX4 further attenuated hepatic TLR4/NF-κB signaling. This probiotic-based enzyme delivery offers a precise, microbiome-modulating strategy to interrupt pyroptotic amplification, with strong translational promise for sepsis management.}
}