EcN OMV and Alzheimer's disease

Gut microbiota dysbiosis is a driving factor in Alzheimer's disease (AD), yet the mechanisms behind gut-brain communication remain elusive. Emerging evidence highlights that bacterial outer membrane vesicles (OMVs) are critical mediators of the microbiota-host communication. Here, we observed a reduction in a gut bacterial strain resembling the probiotic Escherichia coli Nissle 1917 (EcN) in AD patients and its levels are positively associated cognitive ability. Notably, we pioneer the investigation of OMVs derived from EcN on AD pathology in mice. The OmpA-contained EcN OMVs can be translocated to the brain, reshaping dysregulated immune network. Specifically, EcN OMVs are internalized by glia and neurons, suppressing the glial hyperactivation and restoring synaptic function, thereby reducing Aβ deposition and cognitive deficits. The results further showed OmpA plays an important role in vesicle trafficking and inflammatory pathways and may be the key regulator of the inflammatory mediators in EcN OMVs, modulating the astrocyte-microglia-neuron interactions and functionality. This work discloses the substantial therapeutic potential of the probiotic and its secreted OMVs in intervention and treatment of neurological disorders.肠道菌群失调（gut microbiota dysbiosis）是阿尔茨海默病（Alzheimer's disease, AD）的致病驱动因素，但肠-脑交流的潜在机制仍尚不明确。越来越多的研究证据表明，细菌外膜囊泡（bacterial outer membrane vesicles, OMVs）是菌群与宿主间交流的关键介质。本研究在阿尔茨海默病患者体内发现，一类与益生菌大肠杆菌Nissle 1917（Escherichia coli Nissle 1917, EcN）相似的肠道菌株丰度显著降低，且该菌株的丰度与认知能力呈正相关。值得注意的是，本研究率先探索了EcN来源的OMVs对小鼠AD病理的调控作用。携带外膜蛋白A（Outer Membrane Protein A, OmpA）的EcN OMVs可易位至脑部，重塑失调的免疫网络。具体而言，EcN OMVs可被神经胶质细胞与神经元摄取，抑制胶质细胞过度活化并修复突触功能，进而减少β淀粉样蛋白（Aβ）沉积并改善认知缺陷。研究结果进一步显示，OmpA在囊泡运输与炎症通路中发挥关键作用，或为EcN OMVs中炎症介质的核心调控因子，可调节星形胶质细胞-小胶质细胞-神经元的相互作用与功能。本研究揭示了该益生菌及其分泌的OMVs在神经系统疾病的干预与治疗中具备可观的治疗潜力。