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.contributor.funder	University College Cork	en
dc.contributor.funder	Science Foundation Ireland	en
dc.date.accessioned	2019-11-19T10:20:35Z
dc.date.available	2019-11-19T10:20:35Z
dc.date.issued	2019-03-18
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.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
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.doi	10.1016/j.ebiom.2019.03.029	en
dc.identifier.eissn	2352-3964
dc.identifier.endpage	638	en
dc.identifier.journaltitle	EBioMedicine	en
dc.identifier.startpage	618	en
dc.identifier.uri	https://hdl.handle.net/10468/9066
dc.identifier.volume	44	en
dc.language.iso	en	en
dc.publisher	Elsevier	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.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

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

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