Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland.
Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland.
EBioMedicine. 2018 Dec;38:191-205. doi: 10.1016/j.ebiom.2018.11.010. Epub 2018 Nov 13.
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.
Adult male guinea-pigs were exposed to CIH (6.5% O at nadir, 6 cycles.hour) for 8 h.day for 12 consecutive days.
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.
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.
The Department of Physiology, and APC Microbiome Ireland, UCC.
颈动脉体（外周氧传感器）的敏化是慢性间歇性低氧（CIH）诱导高血压发展的关键。我们试图确定暴露于 CIH（模拟人类睡眠呼吸暂停）是否会对豚鼠的心肺控制产生不利影响，豚鼠的颈动脉体对缺氧不敏感。我们推断，CIH 引起的肠道微生物群破坏会引起心肺疾病。
成年雄性豚鼠连续 12 天每天暴露于 CIH（最低点 6.5%O，6 个循环/小时）8 小时。
暴露于 CIH 的动物粪便微生物种类丰富度降低，拟杆菌门的相对丰度增加，厚壁菌门的相对丰度降低。暴露于 CIH 的动物尿皮质酮和去甲肾上腺素水平不变，但延髓去甲肾上腺素浓度低于假手术组。暴露于 CIH 的动物和假手术组的基础通气量相当；然而，呼吸时相变异、叹息频率和低氧呼吸时的通气量均较低。暴露于 CIH 对基础动脉血压没有影响，但在苯肾上腺素引起的升压反应中，β-肾上腺素能受体依赖性心动过速和心动过缓减弱与假手术对照组相比是明显的。
增加颈动脉体化学传入信号似乎是 CIH 诱导高血压和升高的化学反射性呼吸控制发展所必需的，这在哺乳动物中通常与缺氧敏感的颈动脉体有关。然而，我们发现，适度的 CIH 暴露会改变肠道微生物群落的丰富度和组成、脑干神经化学和心率的自主控制，而与颈动脉体敏化无关，这表明通过微生物群-肠道-脑干轴来调节呼吸和自主平衡。这些发现与人类睡眠呼吸障碍有关。
生理学系和 APC 微生物组爱尔兰，UCC。
