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

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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.date.accessioned 2019-08-07T08:02:01Z
dc.date.available 2019-08-07T08:02:01Z
dc.date.issued 2018-12-01
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.volume 38 en
dc.identifier.startpage 191 en
dc.identifier.endpage 205 en
dc.identifier.uri http://hdl.handle.net/10468/8286
dc.identifier.doi 10.1016/j.ebiom.2018.11.010 en
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.format.mimetype application/pdf 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
dc.internal.authorcontactother Ken O'Halloran, Department of Physiology, 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.description.status Peer reviewed en
dc.identifier.journaltitle EBioMedicine en
dc.internal.IRISemailaddress k.ohalloran@ucc.ie en
dc.identifier.eissn 2352-3964


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© 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/). Except where otherwise noted, this item's license is described as © 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/).
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