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.