Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

View ORCID ProfileLesley Hoyles, Tom Snelling, Umm-Kulthum Umlai, View ORCID ProfileJeremy K. Nicholson, View ORCID ProfileSimon R. Carding, View ORCID ProfileRobert C. Glen, View ORCID ProfileSimon McArthur
doi: https://doi.org/10.1101/170548
Lesley Hoyles
Imperial College London;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lesley Hoyles
  • For correspondence: lesley.hoyles11@imperial.ac.uk
Tom Snelling
Imperial College London;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Umm-Kulthum Umlai
Imperial College London;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeremy K. Nicholson
Imperial College London;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jeremy K. Nicholson
Simon R. Carding
Quadram Institute;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Simon R. Carding
Robert C. Glen
Imperial College London;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Robert C. Glen
Simon McArthur
Queen Mary University of London
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Simon McArthur
  • Abstract
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Background: Gut microbiota composition and function are symbiotically linked with host health, and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognized mechanisms exist by which the microbiome influences the gut--brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesized 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) signaling. 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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted February 07, 2018.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier
Lesley Hoyles, Tom Snelling, Umm-Kulthum Umlai, Jeremy K. Nicholson, Simon R. Carding, Robert C. Glen, Simon McArthur
bioRxiv 170548; doi: https://doi.org/10.1101/170548
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier
Lesley Hoyles, Tom Snelling, Umm-Kulthum Umlai, Jeremy K. Nicholson, Simon R. Carding, Robert C. Glen, Simon McArthur
bioRxiv 170548; doi: https://doi.org/10.1101/170548

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (996)
  • Biochemistry (1485)
  • Bioengineering (941)
  • Bioinformatics (6806)
  • Biophysics (2414)
  • Cancer Biology (1782)
  • Cell Biology (2518)
  • Clinical Trials (106)
  • Developmental Biology (1685)
  • Ecology (2556)
  • Epidemiology (1489)
  • Evolutionary Biology (5006)
  • Genetics (3603)
  • Genomics (4618)
  • Immunology (1159)
  • Microbiology (4228)
  • Molecular Biology (1618)
  • Neuroscience (10753)
  • Paleontology (81)
  • Pathology (236)
  • Pharmacology and Toxicology (407)
  • Physiology (553)
  • Plant Biology (1448)
  • Scientific Communication and Education (410)
  • Synthetic Biology (542)
  • Systems Biology (1870)
  • Zoology (258)