Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer's disease mouse models.
Nat Commun
; 15(1): 3872, 2024 May 08.
Article
in En
| MEDLINE
| ID: mdl-38719797
ABSTRACT
The gut microbiota and microglia play critical roles in Alzheimer's disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-ß (Aß) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aß plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression. We further show that administering Bacteroides fragilis to aged wild-type male and female mice suppresses microglial uptake of Aß1-42 injected into the hippocampus. Depleting murine Bacteroidota with metronidazole decreases amyloid load in aged 5xFAD mice, and activates microglial pathways related to phagocytosis, cytokine signaling, and lysosomal degradation. Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aß clearance and accumulation of amyloid plaques.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phagocytosis
/
Mice, Transgenic
/
Amyloid beta-Peptides
/
Microglia
/
Plaque, Amyloid
/
Disease Models, Animal
/
Alzheimer Disease
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Nat Commun
/
Nature communications
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Type:
Article
Affiliation country:
United States