Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide

Abstract Background Communication 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 du...

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Autores principales:	Lesley Hoyles, Matthew G. Pontifex, Ildefonso Rodriguez-Ramiro, M. Areeb Anis-Alavi, Khadija S. Jelane, Tom Snelling, Egle Solito, Sonia Fonseca, Ana L. Carvalho, Simon R. Carding, Michael Müller, Robert C. Glen, David Vauzour, Simon McArthur
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Trimethylamine N-oxide Trimethylamine Blood–brain barrier Cognition Microbial ecology QR100-130
Acceso en línea:	https://doaj.org/article/c0d2035498a04a8b9ff53c987c2ef532
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spelling	oai:doaj.org-article:c0d2035498a04a8b9ff53c987c2ef5322021-11-28T12:08:09ZRegulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide10.1186/s40168-021-01181-z2049-2618https://doaj.org/article/c0d2035498a04a8b9ff53c987c2ef5322021-11-01T00:00:00Zhttps://doi.org/10.1186/s40168-021-01181-zhttps://doaj.org/toc/2049-2618Abstract Background Communication 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. Results Here, 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. Conclusion Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstractLesley HoylesMatthew G. PontifexIldefonso Rodriguez-RamiroM. Areeb Anis-AlaviKhadija S. JelaneTom SnellingEgle SolitoSonia FonsecaAna L. CarvalhoSimon R. CardingMichael MüllerRobert C. GlenDavid VauzourSimon McArthurBMCarticleTrimethylamine N-oxideTrimethylamineBlood–brain barrierCognitionMicrobial ecologyQR100-130ENMicrobiome, Vol 9, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Trimethylamine N-oxide Trimethylamine Blood–brain barrier Cognition Microbial ecology QR100-130
spellingShingle	Trimethylamine N-oxide Trimethylamine Blood–brain barrier Cognition Microbial ecology QR100-130 Lesley Hoyles Matthew G. Pontifex Ildefonso Rodriguez-Ramiro M. Areeb Anis-Alavi Khadija S. Jelane Tom Snelling Egle Solito Sonia Fonseca Ana L. Carvalho Simon R. Carding Michael Müller Robert C. Glen David Vauzour Simon McArthur Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide
description	Abstract Background Communication 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. Results Here, 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. Conclusion Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstract
format	article
author	Lesley Hoyles Matthew G. Pontifex Ildefonso Rodriguez-Ramiro M. Areeb Anis-Alavi Khadija S. Jelane Tom Snelling Egle Solito Sonia Fonseca Ana L. Carvalho Simon R. Carding Michael Müller Robert C. Glen David Vauzour Simon McArthur
author_facet	Lesley Hoyles Matthew G. Pontifex Ildefonso Rodriguez-Ramiro M. Areeb Anis-Alavi Khadija S. Jelane Tom Snelling Egle Solito Sonia Fonseca Ana L. Carvalho Simon R. Carding Michael Müller Robert C. Glen David Vauzour Simon McArthur
author_sort	Lesley Hoyles
title	Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide
title_short	Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide
title_full	Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide
title_fullStr	Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide
title_full_unstemmed	Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide
title_sort	regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine n-oxide
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c0d2035498a04a8b9ff53c987c2ef532
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Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide

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