Manipulation of gut microbiota blunts the ventilatory response to hypercapnia in adult rats

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dc.contributor.author O'Connor, Karen M.
dc.contributor.author Lucking, Eric F.
dc.contributor.author Golubeva, Anna V.
dc.contributor.author Strain, Conall R.
dc.contributor.author Fouhy, Fiona
dc.contributor.author Cenit, María C.
dc.contributor.author Dhaliwal, Pardeep
dc.contributor.author Bastiaanssen, Thomaz F. S.
dc.contributor.author Burns, David P.
dc.contributor.author Stanton, Catherine
dc.contributor.author Clarke, Gerard
dc.contributor.author Cryan, John F.
dc.contributor.author O'Halloran, Ken D.
dc.date.accessioned 2019-11-19T10:20:35Z
dc.date.available 2019-11-19T10:20:35Z
dc.date.issued 2019-03-18
dc.identifier.citation O'Connor, K.M., Lucking, E.F., Golubeva, A.V., Strain, C.R., Fouhy, F., Cenit, M.C., Dhaliwal, P., Bastiaanssen, T.F., Burns, D.P., Stanton, C. and Clarke, G., 2019. Manipulation of gut microbiota blunts the ventilatory response to hypercapnia in adult rats. EBioMedicine. (20pp). DOI:10.1016/j.ebiom.2019.03.029 en
dc.identifier.volume 44 en
dc.identifier.startpage 618 en
dc.identifier.endpage 638 en
dc.identifier.uri http://hdl.handle.net/10468/9066
dc.identifier.doi 10.1016/j.ebiom.2019.03.029 en
dc.description.abstract Background It is increasingly evident that perturbations to the diversity and composition of the gut microbiota have significant consequences for the regulation of integrative physiological systems. There is growing interest in the potential contribution of microbiota-gut-brain signalling to cardiorespiratory control in health and disease. Methods In adult male rats, we sought to determine the cardiorespiratory effects of manipulation of the gut microbiota following a 4-week administration of a cocktail of antibiotics. We subsequently explored the effects of administration of faecal microbiota from pooled control (vehicle) rat faeces, given by gavage to vehicle- and antibiotic-treated rats. Findings Antibiotic intervention depressed the ventilatory response to hypercapnic stress in conscious animals, owing to a reduction in the respiratory frequency response to carbon dioxide. Baseline frequency, respiratory timing variability, and the expression of apnoeas and sighs were normal. Microbiota-depleted rats had decreased systolic blood pressure. Faecal microbiota transfer to vehicle- and antibiotic-treated animals also disrupted the gut microbiota composition, associated with depressed ventilatory responsiveness to hypercapnia. Chronic antibiotic intervention or faecal microbiota transfer both caused significant disruptions to brainstem monoamine neurochemistry, with increased homovanillic acid:dopamine ratio indicative of increased dopamine turnover, which correlated with the abundance of several bacteria of six different phyla. Interpretation Chronic antibiotic administration and faecal microbiota transfer disrupt gut microbiota, brainstem monoamine concentrations and the ventilatory response to hypercapnia. We suggest that aberrant microbiota-gut-brain axis signalling has a modulatory influence on respiratory behaviour during hypercapnic stress. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.uri https://www.sciencedirect.com/science/article/pii/S2352396419301690
dc.rights © 2019 Published by Elsevier B.V. en
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Antibiotics en
dc.subject Faecal microbiota transfer en
dc.subject Breathing en
dc.subject Hypercapnia en
dc.subject Cardiovascular en
dc.subject Vagus en
dc.subject Neurochemistry en
dc.subject Intestinal permeability en
dc.subject Microbiota en
dc.title Manipulation of gut microbiota blunts the ventilatory response to hypercapnia in adult rats en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Ken O'Halloran, Department of Physiology, School of Medicine, University College Cork, Cork, Ireland. +353-21-490-3000 Email: k.ohalloran@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder University College Cork en
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle EBioMedicine en
dc.internal.IRISemailaddress k.ohalloran@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.identifier.eissn 2352-3964


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© 2019 Published by Elsevier B.V. Except where otherwise noted, this item's license is described as © 2019 Published by Elsevier B.V.
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