Imperial College London
Alternate

ProfessorRobertGlen

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Computational Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7912r.glen Website

 
 
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Location

 

362Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hoyles:2021:10.1186/s40168-021-01181-z,
author = {Hoyles, L and Pontifex, MG and Rodriguez-Ramiro, I and Anis-Alavi, MA and Jelane, KS and Snelling, T and Solito, E and Fonseca, S and Carvalho, AL and Carding, SR and Muller, M and Glen, RC and Vauzour, D and McArthur, S},
doi = {10.1186/s40168-021-01181-z},
journal = {Microbiome},
pages = {1--21},
title = {Regulation of blood brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide},
url = {http://dx.doi.org/10.1186/s40168-021-01181-z},
volume = {9},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundCommunication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and L-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied.ResultsHere, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner.ConclusionOur findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function.
AU  - Hoyles,L
AU  - Pontifex,MG
AU  - Rodriguez-Ramiro,I
AU  - Anis-Alavi,MA
AU  - Jelane,KS
AU  - Snelling,T
AU  - Solito,E
AU  - Fonseca,S
AU  - Carvalho,AL
AU  - Carding,SR
AU  - Muller,M
AU  - Glen,RC
AU  - Vauzour,D
AU  - McArthur,S
DO  - 10.1186/s40168-021-01181-z
EP  - 21
PY  - 2021///
SN  - 2049-2618
SP  - 1
TI  - Regulation of blood brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide
T2  - Microbiome
UR  - http://dx.doi.org/10.1186/s40168-021-01181-z
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000722896700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01181-z
UR  - http://hdl.handle.net/10044/1/92852
VL  - 9
ER  -
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