Ma DongXue, Zhang YuXin, Zhang Jia, Shi Jun, Gao ShanHu, Long Fei, Wang Xin, Pu XingYu, Sun Jiayao, Liang Shuang, Cannon Richard D, Villas-Boas Silas, Han Ting-Li
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.
Front Immunol. 2025 May 29;16:1501174. doi: 10.3389/fimmu.2025.1501174. eCollection 2025.
Nissle 1917 (EcN) is one of the most extensively studied nonpathogenic Gram-negative probiotic strains worldwide. Recent research has highlighted the ability of EcN outer membrane vesicles (OMVs) to enhance the phagocytosis and proliferation of RAW264.7 macrophages. However, the impact of EcN-OMVs on M1/M2 polarization and metabolic modulation remains unknown.
In this study, we evaluated the metabolic effects of EcN-OMVs on RAW264.7 macrophage polarization using metabolomic, transcriptomic, and fluxomic approaches.
We found that the RAW264.7 macrophages phagocytosed EcN-OMVs, triggering upregulation of the HIF-1, mTORC1, and NF-κB signaling pathways. This metabolic reprogramming enhanced glycolysis, suppressed the TCA cycle, elevated intracellular reactive oxygen species (ROS), TNF-α, IL-6, IL-1β, ATP, and nitric oxide (NO) production, and promoted macrophage proliferation, migration, invasion, and M1-type polarization.
In summary, this research establishes a theoretical foundation for utilizing probiotic OMVs in immunomodulatory therapeutic applications.
1917年发现的Nissle大肠杆菌（EcN）是全球研究最广泛的非致病性革兰氏阴性益生菌菌株之一。最近的研究强调了EcN外膜囊泡（OMV）增强RAW264.7巨噬细胞吞噬作用和增殖的能力。然而，EcN-OMV对M1/M2极化和代谢调节的影响仍然未知。
在本研究中，我们使用代谢组学、转录组学和通量组学方法评估了EcN-OMV对RAW264.7巨噬细胞极化的代谢影响。
我们发现RAW264.7巨噬细胞吞噬EcN-OMV，触发HIF-1、mTORC1和NF-κB信号通路的上调。这种代谢重编程增强了糖酵解，抑制了三羧酸循环，提高了细胞内活性氧（ROS）、肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β、三磷酸腺苷（ATP）和一氧化氮（NO）的产生，并促进了巨噬细胞的增殖、迁移、侵袭和M1型极化。
总之，本研究为益生菌OMV在免疫调节治疗应用中的利用奠定了理论基础。
