Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier.
Microbiome
; 6(1): 55, 2018 03 21.
Article
em En
| MEDLINE
| ID: mdl-29562936
ABSTRACT
BACKGROUND:
Gut microbiota composition and function are symbiotically linked with host health and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognised mechanisms exist by which the microbiome influences the gut-brain axis modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesised interactions between circulating gut-derived microbial metabolites, and the blood-brain barrier (BBB) also contribute to the gut-brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed.RESULTS:
After demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 µM) on BBB properties in vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signalling.CONCLUSIONS:
Together, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut-brain axis that warrants further attention.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Propionatos
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Bactérias
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Barreira Hematoencefálica
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Trato Gastrointestinal
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Microbioma Gastrointestinal
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article