Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration
Fernández-Calvet, Ariadna (Instituto de Agrobiotecnología)
Matilla-Cuenca, Leticia (Instituto de Agrobiotecnología)
Izco, María (Center for Biomedical Research of La Rioja)
Navarro, Susanna (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Serrano, Miriam (Instituto de Agrobiotecnología)
Ventura, Salvador (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Blesa, Javier (Hospital Universitario HM Puerta del Sur)
Herráiz, Maite (Instituto de Investigación Sanitaria de Navarra)
Alkorta-Aranburu, Gorka (Instituto de Investigación Sanitaria de Navarra)
Galera, Sergio (NASERTIC)
Ruiz de los Mozos, Igor (NASERTIC)
Mansego, María Luisa (Universidad Pública de Navarra)
Toledo-Arana, Alejandro (Instituto de Agrobiotecnología)
Alvarez-Erviti, Lydia (Center for Biomedical Research of La Rioja)
Valle, Jaione (Instituto de Agrobiotecnología)

Data:	2024
Resum:	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. The microbiota of the intestinal tract is considered a large biofilm formed by myriads bacteria that have a considerable impact in health and disease. Here, the authors show that biofilm-associated proteins from intestinal microbiota form amyloid-like structures that exacerbate alpha-synuclein pathologies.
Ajuts:	Agencia Estatal de Investigación PID2021-124248OB-I00 Instituto de Salud Carlos III CPII20/00027 Instituto de Salud Carlos III CP19/00200
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Microbiome ; Biofilms
Publicat a:	Nature communications, Vol. 15 (May 2024) , art. 4150, ISSN 2041-1723

DOI: 10.1038/s41467-024-48309-x
PMID: 38755164

19 p, 6.8 MB

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