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阻塞性睡眠呼吸暂停低通气综合征中的肠道微生物群:与疾病相关的失调和代谢合并症。

Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities.

机构信息

Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China

Respiratory Medicine Center of Fujian Province, Quanzhou 362000, China.

出版信息

Clin Sci (Lond). 2019 Apr 12;133(7):905-917. doi: 10.1042/CS20180891. Print 2019 Apr 15.

Abstract

Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea-hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea-hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5 < AHI ≤ 15 (=40), 15 < AHI ≤ 30 (=23), and AHI ≥ 30 (=30)] and 20 controls (AHI ≤ 5) and determined the microbiome composition via 16S rRNA pyrosequencing and bioinformatics analysis of variable regions 3-4. We measured fasting levels of homocysteine (HCY), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Results revealed gut microbial dysbiosis in several patients with varying severities of OSAHS, reliably separating them from controls with a receiver operating characteristic-area under the curve (ROC-AUC) of 0.789. Functional analysis in the microbiomes of patients revealed alterations; additionally, decreased in short-chain fatty acid (SCFA)-producing bacteria and increased pathogens, accompanied by elevated levels of IL-6. levels correlated with HCY levels. Stratification analysis revealed that the enterotype posed the highest risk for patients with OSAHS. Our results show that the presence of an altered microbiome is associated with HCY among OSAHS patients. These changes in the levels of SCFA affect the levels of pathogens that play a pathophysiological role in OSAHS and related metabolic comorbidities.

摘要

肠道微生物群的改变表现为间歇性缺氧和睡眠片段化,从而模拟阻塞性睡眠呼吸暂停低通气综合征(OSAHS)。在这里,我们试图在 OSAHS 患者的一系列呼吸暂停低通气指数(AHI)范围内首次直接调查肠道微生物失调。我们从 93 名 OSAHS 患者(5<AHI≤15[=40],15<AHI≤30[=23],和 AHI≥30[=30])和 20 名对照者(AHI≤5)中获得粪便样本,并通过 16S rRNA 焦磷酸测序和可变区 3-4 的生物信息学分析来确定微生物组组成。我们测量了空腹同型半胱氨酸(HCY)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平。结果表明,在不同严重程度的 OSAHS 患者中存在肠道微生物失调,可靠地将他们与对照组区分开来,其接受者操作特征曲线下的面积(ROC-AUC)为 0.789。对患者微生物组的功能分析显示存在改变;此外,短链脂肪酸(SCFA)产生菌减少,病原体增加,同时 IL-6 水平升高。HCY 水平与 TNF-α水平相关。分层分析显示,产 enterotype 菌的存在对 OSAHS 患者的风险最高。我们的研究结果表明,微生物组的改变与 OSAHS 患者的 HCY 有关。SCFA 水平的这些变化影响病原体的水平,这些病原体在 OSAHS 及其相关代谢合并症中发挥病理生理作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d13d/6465302/a0e066e3b2b4/cs-133-cs20180891-g1.jpg

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