Yao Qianyi, Liu Tao, Wen Jingtao, Yang Qunfang, Li Yunong, Yan Huang, Zhang Lanfang, Zhu Borong, Tian Ying, Wang Yujie, Yang Xiong, Shi Xinhui, Zhang Haigang, Liu Ya, Li Xiaoli, Shan Wenjun
Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China.
Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, China.
J Control Release. 2025 Oct 10;386:114163. doi: 10.1016/j.jconrel.2025.114163. Epub 2025 Aug 23.
Mortality resulting from sepsis is highly associated with secondary acute lung injury, and although the gut-lung axis is of significant importance, treatment strategies leveraging this understanding remains limited. Here, we developed an Escherichia coli strain named ΔPESI that highly expresses IL-1Ra via outer membrane vesicles (OMVs) and PEGylated this strain through the SpyCatcher-SpyTag system for enhanced activity and colonization. Oral administration of ΔPESI reinforces epithelial barrier integrity in the gut, inhibits inflammatory cascade in the peripheral circulation, modulates macrophage polarization and pyroptosis in the lung, thereby significantly mitigating the dysregulated systemic inflammatory response. Furthermore, ΔPESI exhibits favorable biosafety characteristics, thus demonstrating strong potential for clinical translation. Hence, this study proposes a promising strategy for the oral administration of engineered probiotics to effectively alleviate intestinal and pulmonary inflammatory responses through modulation of the gut-lung crosstalk.
脓毒症导致的死亡率与继发性急性肺损伤高度相关，尽管肠-肺轴非常重要，但基于这一认识的治疗策略仍然有限。在此，我们开发了一种名为ΔPESI的大肠杆菌菌株，该菌株通过外膜囊泡（OMV）高度表达IL-1Ra，并通过SpyCatcher-SpyTag系统对该菌株进行聚乙二醇化处理，以增强其活性和定植能力。口服ΔPESI可增强肠道上皮屏障的完整性，抑制外周循环中的炎症级联反应，调节肺部巨噬细胞的极化和焦亡，从而显著减轻失调的全身炎症反应。此外，ΔPESI具有良好的生物安全特性，因此具有很强的临床转化潜力。因此，本研究提出了一种有前景的策略，即口服工程益生菌，通过调节肠-肺相互作用来有效减轻肠道和肺部的炎症反应。
