Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration

Ariadna Fernández-Calvet, Leticia Matilla-Cuenca, María Izco, Susanna Navarro, Miriam Serrano, Salvador Ventura, Javier Blesa, Maite Herráiz, Gorka Alkorta-Aranburu, Sergio Galera, Igor Ruiz de los Mozos, María Luisa Mansego, Alejandro Toledo-Arana, Lydia Alvarez-Erviti and Jaione Valle ()
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Ariadna Fernández-Calvet: Instituto de Agrobiotecnología (IDAB). CSIC-Gobierno de Navarra
Leticia Matilla-Cuenca: Instituto de Agrobiotecnología (IDAB). CSIC-Gobierno de Navarra
María Izco: Center for Biomedical Research of La Rioja
Susanna Navarro: Universitat Autónoma de Barcelona
Miriam Serrano: Instituto de Agrobiotecnología (IDAB). CSIC-Gobierno de Navarra
Salvador Ventura: Universitat Autónoma de Barcelona
Javier Blesa: Hospital Universitario HM Puerta del Sur, HM Hospitales
Maite Herráiz: University of Navarra
Gorka Alkorta-Aranburu: Instituto de Investigación Sanitaria de Navarra
Sergio Galera: Government of Navarra
Igor Ruiz de los Mozos: Government of Navarra
María Luisa Mansego: Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA
Alejandro Toledo-Arana: Instituto de Agrobiotecnología (IDAB). CSIC-Gobierno de Navarra
Lydia Alvarez-Erviti: Center for Biomedical Research of La Rioja
Jaione Valle: Instituto de Agrobiotecnología (IDAB). CSIC-Gobierno de Navarra

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Age-related neurodegenerative diseases involving amyloid aggregation remain one of the biggest challenges of modern medicine. Alterations in the gastrointestinal microbiome play an active role in the aetiology of neurological disorders. Here, we dissect the amyloidogenic properties of biofilm-associated proteins (BAPs) of the gut microbiota and their implications for synucleinopathies. We demonstrate that BAPs are naturally assembled as amyloid-like fibrils in insoluble fractions isolated from the human gut microbiota. We show that BAP genes are part of the accessory genomes, revealing microbiome variability. Remarkably, the abundance of certain BAP genes in the gut microbiome is correlated with Parkinson’s disease (PD) incidence. Using cultured dopaminergic neurons and Caenorhabditis elegans models, we report that BAP-derived amyloids induce α-synuclein aggregation. Our results show that the chaperone-mediated autophagy is compromised by BAP amyloids. Indeed, inoculation of BAP fibrils into the brains of wild-type mice promote key pathological features of PD. Therefore, our findings establish the use of BAP amyloids as potential targets and biomarkers of α-synucleinopathies.

Date: 2024
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DOI: 10.1038/s41467-024-48309-x

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