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

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cam.issuedOnline2021-11-27
dc.contributor.authorHoyles, Lesley
dc.contributor.authorPontifex, Matthew G
dc.contributor.authorRodriguez-Ramiro, Ildefonso
dc.contributor.authorAnis-Alavi, M Areeb
dc.contributor.authorJelane, Khadija S
dc.contributor.authorSnelling, Tom
dc.contributor.authorSolito, Egle
dc.contributor.authorFonseca, Sonia
dc.contributor.authorCarvalho, Ana L
dc.contributor.authorCarding, Simon R
dc.contributor.authorMüller, Michael
dc.contributor.authorGlen, Robert C
dc.contributor.authorVauzour, David
dc.contributor.authorMcArthur, Simon
dc.contributor.orcidMcArthur, Simon [0000-0001-8521-1808]
dc.date.accessioned2022-01-10T12:44:48Z
dc.date.available2022-01-10T12:44:48Z
dc.date.issued2021-11-27
dc.date.updated2022-01-10T12:44:47Z
dc.description.abstractBACKGROUND: 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.
dc.identifier.doi10.17863/CAM.79924
dc.identifier.eissn2049-2618
dc.identifier.issn2049-2618
dc.identifier.otherPMC8626999
dc.identifier.other34836554
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332474
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1186/s40168-021-01181-z
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2049-2618
dc.sourcenlmid: 101615147
dc.subjectBlood–brain barrier
dc.subjectCognition
dc.subjectTrimethylamine
dc.subjectTrimethylamine N-oxide
dc.subjectAnimals
dc.subjectBlood-Brain Barrier
dc.subjectCognition
dc.subjectMammals
dc.subjectMethylamines
dc.subjectMice
dc.subjectMicrobiota
dc.titleRegulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide.
dc.typeArticle
dcterms.dateAccepted2021-10-18
prism.issueIdentifier1
prism.publicationNameMicrobiome
prism.volume9
pubs.funder-project-idMedical Research Council (MR/L01632X/1)
pubs.funder-project-idAlzheimer's Research UK (ARUK-PPG2016B-6)
pubs.funder-project-idSolvo Biotechnology (ReACTS Program)
pubs.funder-project-idImperial College London (Undergraduate Research Opportunities Programme)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1186/s40168-021-01181-z

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