Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice

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dc.contributor.author Burokas, Aurelijus
dc.contributor.author Arboleya, Silvia
dc.contributor.author Moloney, Rachel D.
dc.contributor.author Peterson, Veronica L.
dc.contributor.author Murphy, Kiera
dc.contributor.author Clarke, Gerard
dc.contributor.author Stanton, Catherine
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Cryan, John F.
dc.date.accessioned 2017-04-26T10:54:04Z
dc.date.available 2017-04-26T10:54:04Z
dc.date.issued 2017-02-24
dc.identifier.citation Burokas, A., Arboleya, S., Moloney, R. D., Peterson, V. L., Murphy, K., Clarke, G., Stanton, C., Dinan, T. G. and Cryan, J. F. (2017) ‘Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice’, Biological Psychiatry. doi:10.1016/j.biopsych.2016.12.031 en
dc.identifier.issn 0006-3223
dc.identifier.uri http://hdl.handle.net/10468/3890
dc.identifier.doi 10.1016/j.biopsych.2016.12.031
dc.description.abstract Background: The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. Methods: C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Results: Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota. Conclusions: Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology. en
dc.description.sponsorship Science Foundation Ireland (SFI Grant Nos. SFI/12/RC/2273; SFI/02/CE/B124; SFI/07/CE/B1368) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier Ltd on behalf of the Society of Biological Psychiatry en
dc.rights © 2017, Society of Biological Psychiatry. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Animal behavior en
dc.subject Anxiety en
dc.subject Microbiota-gut-brain axis en
dc.subject Prebiotics en
dc.subject SCFAs en
dc.subject Stress en
dc.title Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice 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 12 months after publication by request of the publisher. en
dc.check.date 2018-02-24
dc.date.updated 2017-04-12T11:34:04Z
dc.description.version Accepted Version en
dc.internal.rssid 390926579
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Biological Psychiatry en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.internal.bibliocheck In press. Add vol. / issue / page range. Amend citation accordingly.


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© 2017, Society of Biological Psychiatry. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ Except where otherwise noted, this item's license is described as © 2017, Society of Biological Psychiatry. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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