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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.date.accessioned2021-12-15T10:09:32Z
dc.date.available2021-12-15T10:09:32Z
dc.date.issued2021-11-27
dc.date.submitted2021-10-07
dc.identifier.issn2049-2618
dc.identifier.others40168-021-01181-z
dc.identifier.other1181
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331450
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.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectResearch
dc.subjectThe microbiota–gut–brain axis
dc.subjectTrimethylamine N-oxide
dc.subjectTrimethylamine
dc.subjectBlood–brain barrier
dc.subjectCognition
dc.titleRegulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide.
dc.typeArticle
dc.date.updated2021-12-15T10:09:30Z
prism.issueIdentifier1
prism.publicationNameMicrobiome
prism.volume9
dc.identifier.doi10.17863/CAM.78904
dcterms.dateAccepted2021-10-18
rioxxterms.versionofrecord10.1186/s40168-021-01181-z
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMcArthur, Simon [0000-0001-8521-1808]
dc.identifier.eissn2049-2618
pubs.funder-project-idAlzheimer's Research UK (ARUK-PPG2016B-6)
pubs.funder-project-idSolvo Biotechnology (ReACTS Program)
pubs.funder-project-idMedical Research Council (MR/L01632X/1)
pubs.funder-project-idImperial College London (Undergraduate Research Opportunities Programme)
cam.issuedOnline2021-11-27


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