Polyphenols selectively reverse early-life stress-induced behavioural, neurochemical and microbiota changes in the rat

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dc.contributor.author Donoso, Francisco
dc.contributor.author Egerton, Sian
dc.contributor.author Bastiaanssen, Thomaz F. S.
dc.contributor.author Fitzgerald, Patrick
dc.contributor.author Gite, Snehal
dc.contributor.author Fouhy, Fiona
dc.contributor.author Ross, R. Paul
dc.contributor.author Stanton, Catherine
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Cryan, John F.
dc.date.accessioned 2020-04-28T10:44:29Z
dc.date.available 2020-04-28T10:44:29Z
dc.date.issued 2020-04-10
dc.identifier.citation Donoso, F., Egerton, S., Bastiaanssen, T. F. S., Fitzgerald, P., Gite, S., Fouhy, F., Ross, R. P., Stanton, C., Dinan, T. G. and Cryan, J. F. (2020) 'Polyphenols selectively reverse early-life stress-induced behavioural, neurochemical and microbiota changes in the rat', Psychoneuroendocrinology, 116, 104673 (12pp). doi: 10.1016/j.psyneuen.2020.104673 en
dc.identifier.volume 116 en
dc.identifier.startpage 1 en
dc.identifier.endpage 12 en
dc.identifier.issn 0306-4530
dc.identifier.uri http://hdl.handle.net/10468/9880
dc.identifier.doi 10.1016/j.psyneuen.2020.104673 en
dc.description.abstract There is a growing emphasis on the role of the microbiota-gut-brain axis as modulator of host behaviour and as therapeutic target for neuropsychiatric disorders. In addition, accumulating evidence suggests that early-life stress can exert long-lasting changes on the brain and microbiota, and this early adversity is associated with increased risk for developing depression in later life. The maternal separation (MS) model in rats is a robust paradigm to study the effects of early-life stress on the microbiota-gut-brain axis. Recently, we have shown that polyphenols, naturally occurring compounds associated with several health benefits, have anti-stress effects in in vitro models. In this study, we assess the therapeutic potential of a variety of both flavonoid and non-flavonoid polyphenols in reversing the impact of MS on behaviour and the microbiota-gut-brain axis. Rats underwent a dietary intervention with the naturally-derived polyphenols xanthohumol and quercetin, as well as with a phlorotannin extract for 8 weeks. Treatment with polyphenols prevented the depressive and anxiety-like behaviours induced by MS, where xanthohumol effects were correlated with rescue of BDNF plasma levels. In addition, MS resulted in altered brain levels of 5-hydroxyindoleacetic acid (5-HIAA) and dopamine, accompanied by abnormal elevation of plasma corticosterone. Although polyphenols did not reverse neurotransmitter imbalance, xanthohumol normalised corticosterone levels in MS rats. Finally, we explored the impact of MS and polyphenolic diets on the gut microbiota. We observed profound changes in microbial composition and diversity produced by MS condition and by xanthohumol treatment. Moreover, functional prediction analysis revealed that MS results in altered enrichment of pathways associated with microbiota-brain interactions that are significantly reversed by xanthohumol treatment. These results suggest that naturally-derived polyphenols exert antidepressant-like effects in MS rats, which mechanisms could be potentially mediated by HPA regulation, BDNF levels rescue and modulation of the microbiota-gut-brain axis. en
dc.description.sponsorship Department of Agriculture, Food and the Marine, Ireland (Grant Number 13F411) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier Ltd. en
dc.rights © 2020, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license. en
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Polyphenols en
dc.subject Microbiota-gut-brain axis en
dc.subject Early-life en
dc.subject Stress en
dc.title Polyphenols selectively reverse early-life stress-induced behavioural, neurochemical and microbiota changes in the rat en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John F Cryan, Anatomy and 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 2021-04-10
dc.date.updated 2020-04-15T12:17:13Z
dc.description.version Accepted Version en
dc.internal.rssid 510475416
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Department of Agriculture, Food and the Marine, Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Psychoneuroendocrinology en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.identifier.articleid 104673 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.identifier.eissn 1873-3360


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© 2020, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license. Except where otherwise noted, this item's license is described as © 2020, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.
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