Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome

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dc.contributor.authorBoehme, Marcus
dc.contributor.authorvan de Wouw, Marcel
dc.contributor.authorBastiaanssen, Thomaz F. S.
dc.contributor.authorOlavarría-Ramírez, Loreto
dc.contributor.authorLyons, Katriona
dc.contributor.authorFouhy, Fiona
dc.contributor.authorGolubeva, Anna V.
dc.contributor.authorMoloney, Gerard M.
dc.contributor.authorMinuto, Chiara
dc.contributor.authorSandhu, Kiran V.
dc.contributor.authorScott, Karen A.
dc.contributor.authorClarke, Gerard
dc.contributor.authorStanton, Catherine
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorSchellekens, Harriët
dc.contributor.authorCryan, John F.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2019-06-20T11:09:41Z
dc.date.available2019-06-20T11:09:41Z
dc.date.issued2019-05-16
dc.date.updated2019-06-20T10:41:32Z
dc.description.abstractMale middle age is a transitional period where many physiological and psychological changes occur leading to cognitive and behavioural alterations, and a deterioration of brain function. However, the mechanisms underpinning such changes are unclear. The gut microbiome has been implicated as a key mediator in the communication between the gut and the brain, and in the regulation of brain homeostasis, including brain immune cell function. Thus, we tested whether targeting the gut microbiome by prebiotic supplementation may alter microglia activation and brain function in ageing. Male young adult (8 weeks) and middle-aged (10 months) C57BL/6 mice received diet enriched with a prebiotic (10% oligofructose-enriched inulin) or control chow for 14 weeks. Prebiotic supplementation differentially altered the gut microbiota profile in young and middle-aged mice with changes correlating with faecal metabolites. Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice. In addition, a reduction in ageing-induced infiltration of Ly-6Chi monocytes into the brain coupled with a reversal in ageing-related increases in a subset of activated microglia (Ly-6C+) was observed. Taken together, these data highlight a potential pathway by which targeting the gut microbiome with prebiotics can modulate the peripheral immune response and alter neuroinflammation in middle age. Our data highlight a novel strategy for the amelioration of age-related neuroinflammatory pathologies and brain function.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBoehme, M., van de Wouw, M., Bastiaanssen, T. F. S., Olavarría-Ramírez, L., Lyons, K., Fouhy, F., Golubeva, A. V., Moloney, G. M., Minuto, C., Sandhu, K. V., Scott, K. A., Clarke, G., Stanton, C., Dinan, T. G., Schellekens, H. and Cryan, J. F. (2019) 'Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome', Molecular Psychiatry, doi: 10.1038/s41380-019-0425-1en
dc.identifier.doi10.1038/s41380-019-0425-1en
dc.identifier.endpage17en
dc.identifier.issn1476-5578
dc.identifier.journaltitleMolecular Psychiatryen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/8077
dc.language.isoenen
dc.publisherSpringer Nature Publishing AGen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.projectinfo:eu-repo/grantAgreement/RCUK/MRC/MR/N029488/1/GB/AMBROSIAC - A Menu for Brain Responses Opposing Stress-Induced Alterations in Cognition/en
dc.relation.urihttps://www.nature.com/articles/s41380-019-0425-1
dc.rights© Springer Nature Limited 2019. This is a post-peer-review, pre-copyedit version of an article published in Molecular Psychiatry. The final authenticated version is available online at: https://doi.org/10.1038/s41380-019-0425-1en
dc.subjectBrain functionen
dc.subjectGut microbiomeen
dc.subjectGut microbiotaen
dc.subjectPrebioticsen
dc.subjectGut-brain axisen
dc.titleMid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiomeen
dc.typeArticle (peer-reviewed)en
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