Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; CIBER Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
Chest. 2023 Aug;164(2):503-516. doi: 10.1016/j.chest.2023.03.010. Epub 2023 Mar 15.
OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism.
Does OSA in adults associate with the composition and functional potential of the human gut microbiota?
We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.
We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.
OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
阻塞性睡眠呼吸暂停(OSA)是一种常见的睡眠呼吸障碍疾病,与心血管疾病风险增加有关。间歇性上呼吸道阻塞和缺氧是 OSA 的标志,在动物模型中已显示它们会导致肠道微生物群落组成发生重大变化,并且随后将粪便移植到其他动物中会引起血压和葡萄糖代谢的变化。
成人 OSA 是否与人类肠道微生物群落的组成和功能潜力有关?
我们使用了来自人群为基础的瑞典心肺生物图像研究中的多达 3570 名 50 至 64 岁个体的呼吸多导睡眠图数据,以及粪便样本的深度 shotgun 宏基因组学,以确定覆盖呼吸暂停和低通气、缺氧时的总睡眠时间以及氧减饱和事件数的三个 OSA 参数与肠道微生物群落组成之间的横断面关联。关于潜在混杂因素的数据收集基于问卷调查、现场人体测量、血浆代谢组学以及与瑞典处方药物登记处的关联。
我们发现所有三个 OSA 参数都与肠道中物种多样性降低有关。此外,在多变量调整分析中,与 OSA 相关的缺氧参数与 128 种肠道细菌物种的相对丰度有关,包括 Blautia obeum 和 Collinsella aerofaciens 的丰度增加。后一种物种也与收缩压升高独立相关。此外,睡眠期间缺氧的累积时间与参与九个肠道微生物群落代谢途径的基因丰度有关,包括从乳酸产生丙酸。最后,我们观察到两种具有相反关联的具有异质性的血浆代谢物组,分别与与缺氧参数呈正相关和负相关的物种有关。
与 OSA 相关的缺氧,而不是呼吸暂停/低通气的次数,与特定的肠道微生物物种和功能有关。我们的发现为未来研究 OSA 的肠道微生物群介导的健康影响奠定了基础。