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Hoyles L, Pontifex MG, Rodriguez-Ramiro I, et al. Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome. 2021;9(1):235doi: 10.1186/s40168-021-01181-z.
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., & McArthur, S. (2021). Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome, 9(1), 235. https://doi.org/10.1186/s40168-021-01181-z
Hoyles, Lesley, et al. "Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide." Microbiome vol. 9,1 (2021): 235. doi: https://doi.org/10.1186/s40168-021-01181-z
Hoyles L, 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, McArthur S. Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome. 2021 Nov 27;9(1):235. doi: 10.1186/s40168-021-01181-z. PMID: 34836554; PMCID: PMC8626999.
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Microbiome. 2021 Nov 27;9(1):235. doi: 10.1186/s40168-021-01181-z.

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

Microbiome

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

Affiliations

  1. Department of Biosciences, School of Science and Technology, Nottingham Trent University, Clifton, Nottingham, UK. [email protected].
  2. Norwich Medical School, University of East Anglia, Norwich, UK.
  3. Metabolic Syndrome Group, Madrid Institute for Advanced Studies (IMDEA) in Food, E28049, Madrid, Spain.
  4. Institute of Dentistry, Faculty of Medicine & Dentistry, Queen Mary University of London, London, UK.
  5. Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  6. William Harvey Research Institute, Faculty of Medicine & Dentistry, Queen Mary University of London, London, UK.
  7. Dipartimento di Medicina molecolare e Biotecnologie mediche, Federico II University, Naples, Italy.
  8. The Gut Microbes and Health Research Programme, The Quadram Institute, Norwich Research Park, Norwich, UK.
  9. Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, UK.
  10. Institute of Dentistry, Faculty of Medicine & Dentistry, Queen Mary University of London, London, UK. [email protected].

PMID: 34836554 PMCID: PMC8626999 DOI: 10.1186/s40168-021-01181-z

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.

© 2021. The Author(s).

Keywords: Blood–brain barrier; Cognition; Trimethylamine; Trimethylamine N-oxide

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