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

作者：Hoyles, Lesley^*; Snelling, Tom; Umlai, Umm-Kulthum; Nicholson, Jeremy K.; Carding, Simon R.; Glen, Robert C.; McArthur, Simon^*

来源：Microbiome, 2018, 6(1): 55.

DOI：10.1186/s40168-018-0439-y

• HUMAN GUT MICROBIOME
• PROTEIN-COUPLED RECEPTORS
• CHAIN FATTY-ACIDS
• PARKINSONS-DISEASE
• COGNITIVE IMPAIRMENT
• REGRESSIVE AUTISM
• LIPID-METABOLISM
• CACO-2 CELLS
• INFLAMMATION
• BUTYRATE

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 mu 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.

• 出版日期2018-3-21