Kynurenine pathway metabolism and the microbiota-gut-brain axis

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dc.contributor.author Kennedy, Paul J.
dc.contributor.author Cryan, John F.
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Clarke, Gerard
dc.date.accessioned 2018-01-19T13:08:40Z
dc.date.available 2018-01-19T13:08:40Z
dc.date.issued 2016-07-05
dc.identifier.citation Kennedy, P. J., Cryan, J. F., Dinan, T. G. and Clarke, G. (2016) 'Kynurenine pathway metabolism and the microbiota-gut-brain axis', Neuropharmacology, 112, pp. 399-412. doi:10.1016/j.neuropharm.2016.07.002 en
dc.identifier.volume 112 en
dc.identifier.startpage 399 en
dc.identifier.endpage 412 en
dc.identifier.issn 0028-3908
dc.identifier.uri http://hdl.handle.net/10468/5302
dc.identifier.doi 10.1016/j.neuropharm.2016.07.002
dc.description.abstract It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gut microbiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gut microbiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gut microbiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gut microbiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gut microbiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside. en
dc.description.sponsorship Health Research Board (Grant number HRA-POR-2014-64); Brain and Behavior Research Foundation (Grant Number 20771) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier Ltd. en
dc.rights © 2016, 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 Tryptophan en
dc.subject Kynurenine en
dc.subject Stress en
dc.subject Immune system en
dc.subject Microbiota-gut-brain-axis en
dc.subject Behaviour en
dc.title Kynurenine pathway metabolism and the microbiota-gut-brain axis en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Gerard Clarke, Psychiatry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: g.clarke@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2018-01-18T12:53:05Z
dc.description.version Accepted Version en
dc.internal.rssid 422302505
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Health Research Board en
dc.contributor.funder Brain and Behavior Research Foundation en
dc.contributor.funder Seventh Framework Programme en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Neuropharmacology en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress G.Clarke@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
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/613979/EU/Microbiome Influence on Energy balance and Brain Development-Function Put into Action to Tackle Diet-related Diseases and Behavior./MYNEWGUT en


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© 2016, 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 © 2016, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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