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

Hoyles, L ORCID: https://orcid.org/0000-0002-6418-342X, Pontifex, MG, Rodriguez-Ramiro, I, Anis-Alavi, MA, Jelane, KS, Snelling, T, Solito, E, Fonseca, S, Carvalho, AL, Carding, SR, Müller, M, Glen, RC, Vauzour, D and McArthur, S, 2021. Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome, 9: 235. ISSN 2049-2618

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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.

Item Type:	Journal article
Publication Title:	Microbiome
Creators:	Hoyles, L., Pontifex, M.G., Rodriguez-Ramiro, I., Anis-Alavi, M.A., Jelane, K.S., Snelling, T., Solito, E., Fonseca, S., Carvalho, A.L., Carding, S.R., Müller, M., Glen, R.C., Vauzour, D. and McArthur, S.
Publisher:	BMC
Date:	27 November 2021
Volume:	9
ISSN:	2049-2618
Identifiers:	Number Type 10.1186/s40168-021-01181-z DOI 1480090 Other
Rights:	© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	21 Oct 2021 09:37
Last Modified:	30 Nov 2021 11:56
URI:	https://irep.ntu.ac.uk/id/eprint/44485

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