<EM >PROTEUS MIRABILLIS</EM>–DERIVED OUTER MEMBRANE VESICLES: POTENTIAL CONTRIBUTORS TO EARLY PARKINSON’S DISEASE MECHANISMS

Parkinson’s disease (PD) is characterized by progressive motor dysfunction and diverse non-motor symptoms. Substantial evidence indicates that intestinal dysbiosis is associated with PD, suggesting a contribution of the gut–brain axis to its pathogenesis. Bacterial extracellular vesicles (BEVs) have emerged as mediators of the microbiota–host interaction with a potential role in PD pathogenesis. This study examines the role of outer membrane vesicles (OMVs) derived from Proteus mirabilis (Pm-OMVs), a bacteria associated with gut dysbiosis in individuals with PD, using in vivo and in vitro models.
Following the culture of P. mirabilis, OMVs were isolated and subsequently characterized in terms of their morphological and biophysical properties by Western blotting, cryo-electron microscopy, and nanoparticle tracking analysis. In vitro, glial BV-2 cells and neuronal SH-SY5Y cells treated with Pm-OMVs showed decreased cell viability, increased cytotoxicity, and apoptosis. In vivo, biodistribution experiments showed wide distribution in several organs, including the brain. Using a neuromelanin-accumulating (tgNM) mouse model for PD, we describe the effects of Pm-OMVs administration in the parkinsonian phenotype of these mice compared to age- and sex-matched wild-type mice.
Altogether, this work strengthens the evidence for the involvement of BEVs in PD pathophysiology, possibly through disruption of the gut–brain axis. Understanding the interaction between microbial vesicles and the nervous system may open new avenues for early diagnosis or microbiota-targeted strategies in PD.