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Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier.


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 ?M) 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.

SUBMITTER: Hoyles L 

PROVIDER: S-EPMC5863458 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier.

Hoyles Lesley L   Snelling Tom T   Umlai Umm-Kulthum UK   Nicholson Jeremy K JK   Carding Simon R SR   Glen Robert C RC   McArthur Simon S  

Microbiome 20180321 1


<h4>Background</h4>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 contr  ...[more]

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