Microbiota-related changes in bile acid and tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism

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dc.contributor.author Golubeva, Anna V.
dc.contributor.author Joyce, Susan A.
dc.contributor.author Moloney, Gerard M.
dc.contributor.author Burokas, Aurelijus
dc.contributor.author Sherwin, Eoin
dc.contributor.author Arboleya, Silvia
dc.contributor.author Flynn, Ian
dc.contributor.author Khochanskiy, Dmitry
dc.contributor.author Moya-Pérez, Angela
dc.contributor.author Peterson, Veronica L.
dc.contributor.author Rea, Kieran
dc.contributor.author Murphy, Kiera
dc.contributor.author Makarova, Olga
dc.contributor.author Buravkov, Sergey
dc.contributor.author Hyland, Niall P.
dc.contributor.author Stanton, Catherine
dc.contributor.author Clarke, Gerard
dc.contributor.author Gahan, Cormac G.
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Cryan, John F.
dc.date.accessioned 2017-12-08T13:33:41Z
dc.date.available 2017-12-08T13:33:41Z
dc.date.issued 2017-10-13
dc.identifier.citation Golubeva, A. V., Joyce, S. A., Moloney, G., Burokas, A., Sherwin, E., Arboleya, S., Flynn, I., Khochanskiy, D., Moya-Pérez, A., Peterson, V., Rea, K., Murphy, K., Makarova, O., Buravkov, S., Hyland, N. P., Stanton, C., Clarke, G., Gahan, C. G. M., Dinan, T. G. and Cryan, J. F. (2017) 'Microbiota-related changes in bile acid and tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism', EBioMedicine, 24, pp. 166-178. doi: 10.1016/j.ebiom.2017.09.020 en
dc.identifier.volume 24
dc.identifier.startpage 166
dc.identifier.endpage 178
dc.identifier.issn 2352-3964
dc.identifier.uri http://hdl.handle.net/10468/5135
dc.identifier.doi 10.1016/j.ebiom.2017.09.020
dc.description.abstract Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+ Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut – namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor. en
dc.description.sponsorship Science Foundation Ireland/ European Commission (16/ERAHDHL/3358) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier B.V. en
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S2352396417303742
dc.rights © 2017, the Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject Autism en
dc.subject BTBR mouse en
dc.subject Gut microbiota en
dc.subject Intestinal permeability en
dc.subject Intestinal transit en
dc.subject Bile acids en
dc.subject Serotonin en
dc.subject Tryptophan en
dc.title Microbiota-related changes in bile acid and tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John 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.description.version Published Version en
dc.internal.rssid 424084026
dc.contributor.funder European Commission
dc.contributor.funder Science Foundation Ireland
dc.description.status Peer reviewed en
dc.identifier.journaltitle EBioMedicine en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.internal.IRISemailaddress s.joyce@ucc.ie en
dc.internal.IRISemailaddress n.hyland@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/


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© 2017, the Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Except where otherwise noted, this item's license is described as © 2017, the Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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