Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration.
Animals
Gastrointestinal Microbiome
Caenorhabditis elegans
/ metabolism
Humans
Biofilms
/ growth & development
Amyloid
/ metabolism
alpha-Synuclein
/ metabolism
Parkinson Disease
/ metabolism
Mice
Dopaminergic Neurons
/ metabolism
Autophagy
Neurodegenerative Diseases
/ metabolism
Mice, Inbred C57BL
Bacterial Proteins
/ metabolism
Brain
/ metabolism
Synucleinopathies
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 May 2024
16 May 2024
Historique:
received:
06
11
2023
accepted:
26
04
2024
medline:
17
5
2024
pubmed:
17
5
2024
entrez:
16
5
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38755164
doi: 10.1038/s41467-024-48309-x
pii: 10.1038/s41467-024-48309-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4150Subventions
Organisme : Departamento de Educación, Gobierno de Navarra (Department of Education, Government of Navarra)
ID : PC133-134-135 MICROPROGEN
Informations de copyright
© 2024. The Author(s).
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