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 , and reduced arginine and proline metabolism pathways , compared with controls; also, they had increased stage N1 sleep and reduced stages N2 and N3 sleep accompanied by repeated arousals . Analysis of PBMCs using the Kyoto Encyclopedia of Genes and Genomes database showed that the mTOR signaling pathway 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.

中文翻译：

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严重阻塞性睡眠呼吸暂停相关高血压患者的肠道微生物群、睡眠结构和 mTOR 信号通路的干扰

间歇性缺氧和睡眠片段化是阻塞性睡眠呼吸暂停 (OSA) 的病理生理过程，影响肠道微生物群、睡眠结构和 mTOR 信号通路。然而，这些因素在 OSA 相关高血压的发病机制中的参与仍不清楚。因此，本研究调查了 OSA 相关的高血压机制是否受肠道微生物群和 mTOR 信号通路的调节。患者通过多导睡眠图诊断；获得了他们的粪便样本，并通过 16S 核糖体 RNA 焦磷酸测序和生物信息学分析分析了它们的微生物组组成。使用 Illumina RNA 测序分析检查空腹外周血单核细胞 (PBMC) 上的转录基因。我们总共招募了 60 名重度 OSA 患者 [无高血压 (n  = 27) 和高血压 ( n  = 33)] 和 12 个对照（既不是 OSA 也不是高血压）。结果显示，患有高血压的重度 OSA 患者的肠道微生物组发生改变，产生短链脂肪酸的细菌减少,以及减少精氨酸和脯氨酸代谢途径，与对照相比；此外，他们增加了 N1 阶段的睡眠，减少了 N2 和 N3 阶段的睡眠，并伴有反复唤醒. 使用京都基因和基因组百科全书数据库分析 PBMC 表明 mTOR 信号通路是重度 OSA 高血压患者中最重要的差异基因富集途径。我们的研究结果扩展了先前的工作，并表明 mTOR 信号通路的调节可能通过其与肠道微生物群和睡眠结构紊乱的相互作用而参与发展 OSA 相关的高血压。