Gut microbiota regulates blood-cerebrospinal fluid barrier function and Aß pathology.
EMBO J
; 42(17): e111515, 2023 09 04.
Article
em En
| MEDLINE
| ID: mdl-37427561
ABSTRACT
Accumulating evidence indicates that gut microbiota dysbiosis is associated with increased blood-brain barrier (BBB) permeability and contributes to Alzheimer's disease (AD) pathogenesis. In contrast, the influence of gut microbiota on the blood-cerebrospinal fluid (CSF) barrier has not yet been studied. Here, we report that mice lacking gut microbiota display increased blood-CSF barrier permeability associated with disorganized tight junctions (TJs), which can be rescued by recolonization with gut microbiota or supplementation with short-chain fatty acids (SCFAs). Our data reveal that gut microbiota is important not only for the establishment but also for the maintenance of a tight barrier. Also, we report that the vagus nerve plays an important role in this process and that SCFAs can independently tighten the barrier. Administration of SCFAs in AppNL-G-F mice improved the subcellular localization of TJs at the blood-CSF barrier, reduced the ß-amyloid (Aß) burden, and affected microglial phenotype. Altogether, our results suggest that modulating the microbiota and administering SCFAs might have therapeutic potential in AD via blood-CSF barrier tightening and maintaining microglial activity and Aß clearance.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Microbiota
/
Microbioma Gastrointestinal
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article