Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations

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dc.contributor.author van de Wouw, Marcel
dc.contributor.author Boehme, Marcus
dc.contributor.author Lyte, Joshua M.
dc.contributor.author Wiley, Niamh
dc.contributor.author Strain, Conall
dc.contributor.author O'Sullivan, Orla
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 2020-02-18T16:35:35Z
dc.date.available 2020-02-18T16:35:35Z
dc.date.issued 2018-07-01
dc.identifier.citation van de Wouw, M., Boehme, M., Lyte, J. M., Wiley, N., Strain, C., O'Sullivan, O., Clarke, G., Stanton, C., Dinan, T. G. and Cryan, J. F. (2018) 'Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations', The Journal of Physiology, 596(20), pp. 4923-4944. doi: 10.1113/jp276431 en
dc.identifier.volume 596 en
dc.identifier.issued 20 en
dc.identifier.startpage 4923 en
dc.identifier.endpage 4944 en
dc.identifier.issn 0022-3751
dc.identifier.uri http://hdl.handle.net/10468/9664
dc.identifier.doi 10.1113/jp276431 en
dc.description.abstract There is a growing recognition of the involvement of the gastrointestinal microbiota in the regulation of physiology and behaviour. Microbiota‐derived metabolites play a central role in the communication between microbes and their host, with short‐chain fatty acids (SCFAs) being perhaps the most studied. SCFAs are primarily derived from fermentation of dietary fibres and play a pivotal role in host gut, metabolic and immune function. All these factors have previously been demonstrated to be adversely affected by stress. Therefore, we sought to assess whether SCFA supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixture of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3 weeks of repeated psychosocial stress, followed by a comprehensive behavioural analysis. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota composition were assessed. SCFA treatment alleviated psychosocial stress‐induced alterations in reward‐seeking behaviour, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addition, SCFAs exhibited behavioural test‐specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress‐induced increases in body weight gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota composition. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota‐targeted therapies for stress‐related disorders. en
dc.description.sponsorship Science Foundation Ireland (SFI (15/JP-HDHL/3270; JPI-HDHL-NutriCog project ‘AMBROSIAC) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Wiley en
dc.relation.uri https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP276431
dc.rights © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society; This is the peer reviewed version of the following article: (2018), Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations. J Physiol, 596: 4923-4944, which has been published in final form at https://doi.org/10.1113/JP276431 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. en
dc.subject Gut microbiota en
dc.subject Behaviour en
dc.subject Chronic stress en
dc.title Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations 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.date.updated 2020-02-18T16:23:55Z
dc.description.version Accepted Version en
dc.internal.rssid 503136250
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal of Physiology en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.internal.IRISemailaddress marcus.boehme@ucc.ie en
dc.internal.IRISemailaddress g.clarke@ucc.ie en
dc.internal.IRISemailaddress catherine.stanton@ucc.ie en
dc.internal.IRISemailaddress t.dinan@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/ en


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