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.authorBurokas, Aurelijus
dc.contributor.authorArboleya, Silvia
dc.contributor.authorMoloney, Rachel D.
dc.contributor.authorPeterson, Veronica L.
dc.contributor.authorMurphy, Kiera
dc.contributor.authorClarke, Gerard
dc.contributor.authorStanton, Catherine
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2017-04-26T10:54:04Z
dc.date.available2017-04-26T10:54:04Z
dc.date.issued2017-02-24
dc.date.updated2017-04-12T11:34:04Z
dc.description.abstractBackground: 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.sponsorshipScience Foundation Ireland (SFI Grant Nos. SFI/12/RC/2273; SFI/02/CE/B124; SFI/07/CE/B1368)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBurokas, 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, 82(7), 472-487. doi:10.1016/j.biopsych.2016.12.031en
dc.identifier.doi10.1016/j.biopsych.2016.12.031
dc.identifier.endpage487
dc.identifier.issn0006-3223
dc.identifier.issued7
dc.identifier.journaltitleBiological Psychiatryen
dc.identifier.startpage472
dc.identifier.urihttps://hdl.handle.net/10468/3890
dc.identifier.volume82
dc.language.isoenen
dc.publisherElsevier Ltd on behalf of the Society of Biological Psychiatryen
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.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectAnimal behavioren
dc.subjectAnxietyen
dc.subjectMicrobiota-gut-brain axisen
dc.subjectPrebioticsen
dc.subjectSCFAsen
dc.subjectStressen
dc.titleTargeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in miceen
dc.typeArticle (peer-reviewed)en
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