Clinical and translational medicine · 2026
Engineered probiotics platform for resolvin E1 biosynthesis confers protection against inflammatory disease.
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Li Xiaoxiao, Lin Jiejing, Liu Qingqing, Wu Yiqun, Wu Qian, Zhao Zewei, Cai Yi, Lin Shengliang, Zheng Zijie, Chen Xinpan, Li Jin, Yang Zhonghan
Аннотация
BACKGROUND: The resolution of inflammation is actively driven by omega-3 polyunsaturated fatty acids (PUFAs) via their specialized pro-resolving mediator (SPM) derivatives, including resolvin E1 (RvE1), whose role has been well established. However, clinical application of these mediators is hampered by inherent instability and elevated production costs.
METHODS: To surmount these obstacles, we have engineered a biosynthetic platform based on the probiotic Escherichia coli Nissle 1917 (EcN) that enables controlled, sustained RvE1 production through inducible expression of COX2 and 5-LOX, designated EcN-RvE1. The catalytic capacity, intestinal persistence, and therapeutic efficacy of the platform were evaluated in vitro and in LPS-induced acute inflammation and DSS-induced colitis murine models.
RESULTS: In this study, we validate the capacity of EcN-RvE1 to catalyse the conversion of eicosapentaenoic acid (EPA) to RvE1 and confirm its ability to achieve long-term intestinal persistence. In murine models of acute inflammation and colitis, EcN-RvE1 exerts marked anti-inflammatory and tissue-protective effects, which are mediated by the regulation of inflammatory cytokine expression and the amelioration of gut microbiota dysbiosis. Moreover, EcN-RvE1 using Euglena gracilis as a photosynthetic protist-based source of PUFAs also exhibits protective anti-inflammatory activity.
CONCLUSION: Collectively, we report a probiotic engineering platform for the biosynthesis of RvE1, offering a novel strategy for harnessing the anti-inflammatory potential of PUFAs derivatives in clinical settings.
METHODS: To surmount these obstacles, we have engineered a biosynthetic platform based on the probiotic Escherichia coli Nissle 1917 (EcN) that enables controlled, sustained RvE1 production through inducible expression of COX2 and 5-LOX, designated EcN-RvE1. The catalytic capacity, intestinal persistence, and therapeutic efficacy of the platform were evaluated in vitro and in LPS-induced acute inflammation and DSS-induced colitis murine models.
RESULTS: In this study, we validate the capacity of EcN-RvE1 to catalyse the conversion of eicosapentaenoic acid (EPA) to RvE1 and confirm its ability to achieve long-term intestinal persistence. In murine models of acute inflammation and colitis, EcN-RvE1 exerts marked anti-inflammatory and tissue-protective effects, which are mediated by the regulation of inflammatory cytokine expression and the amelioration of gut microbiota dysbiosis. Moreover, EcN-RvE1 using Euglena gracilis as a photosynthetic protist-based source of PUFAs also exhibits protective anti-inflammatory activity.
CONCLUSION: Collectively, we report a probiotic engineering platform for the biosynthesis of RvE1, offering a novel strategy for harnessing the anti-inflammatory potential of PUFAs derivatives in clinical settings.