Abstract

Intermittent hypoxia and sleep fragmentation are pathophysiological processes involved in obstructive sleep apnea (OSA) which affect gut microbiota, sleep architecture, and mTOR signaling pathway. However, the involvement of these elements in the pathogenesis mechanism of OSA-associated hypertension remains unclear. Therefore, this study investigated whether the OSA-associated hypertension mechanism is regulated by the gut microbiota and mTOR signaling pathway. Patients were diagnosed by polysomnography; their fecal samples were obtained and analyzed for their microbiome composition by 16S ribosomal RNA pyrosequencing and bioinformatics analysis. Transcript genes on fasting peripheral blood mononuclear cells (PBMCs) were examined using Illumina RNA-sequencing analysis. Totally, we enrolled 60 patients with severe OSA [without hypertension (n = 27) and with hypertension (n = 33)] and 12 controls (neither OSA nor hypertension). Results revealed that severe-OSA patients with hypertension had an altered gut microbiome, decreased short-chain fatty acid-producing bacteria (P < 0.05), and reduced arginine and proline metabolism pathways (P=0.001), compared with controls; also, they had increased stage N1 sleep and reduced stages N2 and N3 sleep accompanied by repeated arousals (P < 0.05). Analysis of PBMCs using the Kyoto Encyclopedia of Genes and Genomes database showed that the mTOR signaling pathway (P=0.006) was the most important differential gene-enriched pathway in severe-OSA patients with hypertension. Our findings extend prior work and suggest a possibility that the regulation of the mTOR signaling pathway is involved in developing OSA-associated hypertension through its interaction with the disturbance of the gut microbiome and sleep architecture.

Highlights

  • Obstructive sleep apnea (OSA) is a common clinical sleep disorder affecting the entire body, and it is related to the increased morbidity and mortality of cardiovascular and cerebrovascular diseases [1]

  • We hypothesized that the changes in the gut microbiota and mechanistic target of rapamycin (mTOR) signaling pathway in patients with OSA are involved in developing OSA-associated hypertension. us, we investigated whether the gut microbiota regulates the mechanism of OSA-associated hypertension, sleep architecture, and mTOR signaling pathway by evaluating the gut microbiota, polysomnography (PSG) data, and mTOR levels of peripheral blood mononuclear cells (PBMCs) of severeOSA patients with hypertension and those without hypertension

  • N1 sleep stage, arousal index in NREM, total sleep arousal index, apnea-hypopnea index, obstructive apnea index, central apnea index, mixed apnea index, hypopnea index, oxygen desaturation index, blood pressure elevation index, and the highest systolic blood pressure in the non-OSA group were significantly lower than the OSA group and the OSA-HTN group (Table 2)

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Summary

Introduction

Obstructive sleep apnea (OSA) is a common clinical sleep disorder affecting the entire body, and it is related to the increased morbidity and mortality of cardiovascular and cerebrovascular diseases [1]. Continuous positive airway pressure (CPAP) treatment can substantially reduce the blood pressure of patients with OSA and hypertension (OSAHTN), especially those with refractory hypertension [3, 4]. CPAP treatment has a protective effect on the neurocognition of patients with OSA whether gut microbiota is involved in the neurocognitive physiological mechanism of OSA unclearly [6]. Ey significantly affect the onset of obesity, cardiometabolic abnormalities, and mental illness [7]. These lesions can be seen in patients with OSA

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