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

dc.contributor.authorLucking, Eric F.
dc.contributor.authorO'Connor, Karen M.
dc.contributor.authorStrain, Conall R.
dc.contributor.authorFouhy, Fiona
dc.contributor.authorBastiaanssen, Thomaz F. S.
dc.contributor.authorBurns, David P.
dc.contributor.authorGolubeva, Anna V.
dc.contributor.authorStanton, Catherine
dc.contributor.authorClarke, Gerard
dc.contributor.authorCryan, John F.
dc.contributor.authorO'Halloran, Ken D.
dc.contributor.funderUniversity College Corken
dc.date.accessioned2019-08-07T08:02:01Z
dc.date.available2019-08-07T08:02:01Z
dc.date.issued2018-12-01
dc.description.abstractBackground 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.sponsorshipUCC (Department of Physiology, APC Microbiome Ireland)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLucking, 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.2018.11.010en
dc.identifier.doi10.1016/j.ebiom.2018.11.010en
dc.identifier.eissn2352-3964
dc.identifier.endpage205en
dc.identifier.journaltitleEBioMedicineen
dc.identifier.startpage191en
dc.identifier.urihttps://hdl.handle.net/10468/8286
dc.identifier.volume38en
dc.language.isoenen
dc.publisherElsevier B.V.en
dc.relation.urihttps://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.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectChronic intermittent hypoxiaen
dc.subjectHypertensionen
dc.subjectCardiorespiratory controlen
dc.subjectMicrobiomeen
dc.subjectGuinea-pigen
dc.titleChronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigsen
dc.typeArticle (peer-reviewed)en
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