dc.contributor.author	Lucking, Eric F.
dc.contributor.author	O'Connor, Karen M.
dc.contributor.author	Strain, Conall R.
dc.contributor.author	Fouhy, Fiona
dc.contributor.author	Bastiaanssen, Thomaz F. S.
dc.contributor.author	Burns, David P.
dc.contributor.author	Golubeva, Anna V.
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.date.accessioned	2019-08-07T08:02:01Z
dc.date.available	2019-08-07T08:02:01Z
dc.date.issued	2018-12-01
dc.description.abstract	Background Carotid body (peripheral oxygen sensor) sensitisation is pivotal in the development of chronic intermittent hypoxia (CIH)-induced hypertension. We sought to determine if exposure to CIH, modelling human sleep apnoea, adversely affects cardiorespiratory control in guinea-pigs, a species with hypoxia-insensitive carotid bodies. We reasoned that CIH-induced disruption of gut microbiota would evoke cardiorespiratory morbidity. Methods Adult male guinea-pigs were exposed to CIH (6.5% O2 at nadir, 6 cycles.hour−1) for 8 h.day−1 for 12 consecutive days. Findings CIH-exposed animals established reduced faecal microbiota species richness, with increased relative abundance of Bacteroidetes and reduced relative abundance of Firmicutes bacteria. Urinary corticosterone and noradrenaline levels were unchanged in CIH-exposed animals, but brainstem noradrenaline concentrations were lower compared with sham. Baseline ventilation was equivalent in CIH-exposed and sham animals; however, respiratory timing variability, sigh frequency and ventilation during hypoxic breathing were all lower in CIH-exposed animals. Baseline arterial blood pressure was unaffected by exposure to CIH, but β-adrenoceptor-dependent tachycardia and blunted bradycardia during phenylephrine-induced pressor responses was evident compared with sham controls. Interpretation Increased carotid body chemo-afferent signalling appears obligatory for the development of CIH-induced hypertension and elevated chemoreflex control of breathing commonly reported in mammals, with hypoxia-sensitive carotid bodies. However, we reveal that exposure to modest CIH alters gut microbiota richness and composition, brainstem neurochemistry, and autonomic control of heart rate, independent of carotid body sensitisation, suggesting modulation of breathing and autonomic homeostasis via the microbiota-gut-brainstem axis. The findings have relevance to human sleep-disordered breathing.	en
dc.description.sponsorship	UCC (Department of Physiology, APC Microbiome Ireland)	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Lucking, E.F., O'Connor, K.M., Strain, C.R., Fouhy, F., Bastiaanssen, T.F., Burns, D.P., Golubeva, A.V., Stanton, C., Clarke, G., Cryan, J.F. and O'Halloran, K.D., 2018. Chronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigs. EBioMedicine, 38, 191-205. DOI: 10.1016/j.ebiom.2018.11.010	en
dc.identifier.doi	10.1016/j.ebiom.2018.11.010	en
dc.identifier.eissn	2352-3964
dc.identifier.endpage	205	en
dc.identifier.journaltitle	EBioMedicine	en
dc.identifier.startpage	191	en
dc.identifier.uri	https://hdl.handle.net/10468/8286
dc.identifier.volume	38	en
dc.language.iso	en	en
dc.publisher	Elsevier B.V.	en
dc.relation.uri	https://www.sciencedirect.com/science/article/pii/S2352396418305036?via%3Dihub
dc.rights	© 2018 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	https://creativecommons.org/licenses/by-nc-nd/4.0/	en
dc.subject	Chronic intermittent hypoxia	en
dc.subject	Hypertension	en
dc.subject	Cardiorespiratory control	en
dc.subject	Microbiome	en
dc.subject	Guinea-pig	en
dc.title	Chronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigs	en
dc.type	Article (peer-reviewed)	en

Chronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigs

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