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.author Boehme, Marcus
dc.contributor.author van de Wouw, Marcel
dc.contributor.author Bastiaanssen, Thomaz F. S.
dc.contributor.author Olavarría-Ramírez, Loreto
dc.contributor.author Lyons, Katriona
dc.contributor.author Fouhy, Fiona
dc.contributor.author Golubeva, Anna V.
dc.contributor.author Moloney, Gerard M.
dc.contributor.author Minuto, Chiara
dc.contributor.author Sandhu, Kiran V.
dc.contributor.author Scott, Karen A.
dc.contributor.author Clarke, Gerard
dc.contributor.author Stanton, Catherine
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Schellekens, Harriët
dc.contributor.author Cryan, John F.
dc.date.accessioned 2019-06-20T11:09:41Z
dc.date.available 2019-06-20T11:09:41Z
dc.date.issued 2019-05-16
dc.identifier.citation Boehme, 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/s41380-019-0425-1 en
dc.identifier.startpage 1 en
dc.identifier.endpage 17 en
dc.identifier.issn 1476-5578
dc.identifier.uri http://hdl.handle.net/10468/8077
dc.identifier.doi 10.1038/s41380-019-0425-1 en
dc.description.abstract Male 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Springer Nature Publishing AG en
dc.relation.uri https://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/s41380-019-0425-1 en
dc.subject Brain function en
dc.subject Gut microbiome en
dc.subject Gut microbiota en
dc.subject Prebiotics en
dc.subject Gut-brain axis en
dc.title Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John F Cryan, Department Of Anatomy & Neuroscience, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.cryan@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 6 months after publication by request of the publisher en
dc.check.date 2019-11-16
dc.date.updated 2019-06-20T10:41:32Z
dc.description.version Accepted Version en
dc.internal.rssid 489841015
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Molecular Psychiatry en
dc.internal.copyrightchecked No
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.internal.bibliocheck In Press. Update citation, add vol. issue, update page nos. en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/ en
dc.relation.project info:eu-repo/grantAgreement/RCUK/MRC/MR/N029488/1/GB/AMBROSIAC - A Menu for Brain Responses Opposing Stress-Induced Alterations in Cognition/ en

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