Imperial College London
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Professor Lesley Hoyles

Faculty of Medicine, Department of Surgery & Cancer

Visiting Professor
 
 
 
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Contact

 

lesley.hoyles11 Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Stachulski:2022:10.1101/2022.01.11.475932,
author = {Stachulski, AV and Knausenberger, TB-A and Shah, SN and Hoyles, L and McArthur, S},
doi = {10.1101/2022.01.11.475932},
title = {A host–gut microbial co-metabolite of aromatic amino acids, <i>p</i>-cresol glucuronide, promotes blood–brain barrier integrity <i>in vivo</i>},
url = {http://dx.doi.org/10.1101/2022.01.11.475932},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:sec><jats:title>Purpose</jats:title><jats:p>The sequential activity of gut microbial and host processes can exert a powerful modulatory influence on dietary components, as exemplified by the metabolism of the amino acids tyrosine and phenylalanine to <jats:italic>p</jats:italic>-cresol by gut microbes, and then to <jats:italic>p</jats:italic>-cresol glucuronide (pCG) by host enzymes. Although such glucuronide conjugates are classically thought to be biologically inert, there is accumulating evidence that this may not always be the case. We investigated the activity of pCG, studying its interactions with the cerebral vasculature and the brain <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Male C57Bl/6J mice were used to assess blood–brain barrier (BBB) permeability and whole brain transcriptomic changes in response to pCG treatment. Effects were then further explored using the human cerebromicrovascular endothelial cell line hCMEC/D3, assessing paracellular permeability, transendothelial electrical resistance and barrier protein expression.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Mice exposed to pCG showed reduced BBB permeability and significant changes in whole brain transcriptome expression. Surprisingly, treatment of hCMEC/D3 cells with pCG had no notable effects until co-administered with bacterial lipopolysaccharide, at which point it was able to prevent the permeabilising effects of endotoxin. Further analysis suggested that pCG acts as an antagonist at the principal lipopolysaccharide receptor TLR4.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The amino acid phase II metaboli
AU  - Stachulski,AV
AU  - Knausenberger,TB-A
AU  - Shah,SN
AU  - Hoyles,L
AU  - McArthur,S
DO  - 10.1101/2022.01.11.475932
PY  - 2022///
TI  - A host–gut microbial co-metabolite of aromatic amino acids, <i>p</i>-cresol glucuronide, promotes blood–brain barrier integrity <i>in vivo</i>
UR  - http://dx.doi.org/10.1101/2022.01.11.475932
ER  -
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