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

Hoyles, L. ORCID: 0000-0002-6418-342X, Snelling, T., Umlai, U.-K., Nicholson, J.K., Carding, S.R., Glen, R.C. and McArthur, S., 2018. Microbiome–host systems interactions: protective effects of propionate upon the blood–brain barrier. Microbiome, 6: 55. ISSN 2049-2618

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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.

Item Type: Journal article
Publication Title: Microbiome
Creators: Hoyles, L., Snelling, T., Umlai, U.-K., Nicholson, J.K., Carding, S.R., Glen, R.C. and McArthur, S.
Publisher: BioMed Central Ltd.
Date: 21 March 2018
Volume: 6
ISSN: 2049-2618
Identifiers:
NumberType
10.1186/s40168-018-0439-yDOI
439Publisher Item Identifier
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 07 Aug 2018 10:21
Last Modified: 07 Aug 2018 10:21
URI: http://irep.ntu.ac.uk/id/eprint/34256

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