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by Keyword: virulence factors

Mulet, Maria, Milan, Jose Antonio Sanchez, Lorca, Cristina, Fernandez-Rhodes, Maria, Adrados-Planell, Ana, Castillo, Maria Consuelo Bejarano, Saiz, Laura, Mateos-Moreno, Maria-Victoria, Hase, Yoshiki, Mira, Alex, Rabano, Alberto, del Ser, Teodoro, Kalaria, Raj N, Lagunas, Anna, Mir, Monica, Crespo, Andres, Samitier, Josep, Gallart-Palau, Xavier, Serra, Aida, (2025). Oral Microbiome-Derived Proteins in Brain Extracellular Vesicles Circulate and Tie to Specific Dysbiotic and Neuropathological Profiles in Age-Related Dementias Molecular & Cellular Proteomics 24, 101464

The involvement of the oral microbiome (OM) in the pathophysiology of Alzheimer's disease and vascular dementia has been recognized epidemiologically, but the molecular mechanisms remain elusive. In this study, we uncovered the presence of OM-derived proteins (OMdPs) in brain extracellular vesicles (bEVs) from post-mortem Alzheimer's disease and vascular dementia subjects using unbiased metaproteomics. OMdP circulation in blood EVs was also confirmed in an independent cohort. Our findings also reveal that specific OMdPs are present in bEVs, with their levels varying with disease progression. Peptidome-wide correlation analyses further explored their exchange dynamics and composition within bEVs. In addition, we validated the ability of OM-derived EVs to cross the blood-brain barrier using a blood-brain barrier-on-a-chip model, confirming a potential route for bacterial-derived molecules to reach the central nervous system. Bioinformatics-driven interaction analyses indicated that OMdPs engage with key neuropathological proteins, including amyloid-beta and tau, suggesting a novel mechanism linking dysbiotic OM to dementia. These results provide new insights into the role of the OM in neurodegeneration and highlight OMdPs as potential biomarkers and therapeutic targets.

JTD Keywords: Alzheimers-disease, Communication, Expression, Gut microbiota, Health, Insights, Rna, Virulence factors


Javier-Reyna, R, Avalos-Padilla, Y, Marion, S, (2023). Editorial: Vesicular transport, the actin cytoskeleton and their involvement in virulence mechanisms during host-parasite interaction Frontiers In Cellular And Infection Microbiology 13, 1229067