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阻塞性睡眠呼吸暂停患者口腔微生物群的全基因组宏基因组分析。

Whole-genome metagenomic analysis of the oral microbiota in patients with obstructive sleep apnea.

作者信息

Gao Yinghui, Wang Huanhuan, Hu Yazhuo, Li JianHua, Xu Weihao, Zhao LiBo, Su Xiaofeng, Han Jiming, Li Tianzhi, Fang Xiangqun, Liu Lin

机构信息

PKU-UPenn Sleep Center, Peking University International Hospital, Beijing, 102206, China.

Nursing of Peking University, Beijing, 100191, China.

出版信息

Sleep Breath. 2023 Aug;27(4):1383-1398. doi: 10.1007/s11325-022-02732-w. Epub 2022 Nov 18.

Abstract

PURPOSE

The oral microbiota is closely associated with systemic health, but few studies have investigated the oral microbiota in patients with obstructive sleep apnea (OSA). This study aimed to identify the variation of oral microbiota among patients with severe OSA, and the change of oral microbiota after treatment with continuous positive airway pressure (CPAP).

METHODS

Participants were enrolled in the study from November 2020 to August 2021. Sleep parameters using full nocturnal polysomnography (PSG) were collected on healthy controls, patients with severe OSA, and patients with severe OSA after CPAP treatment for 3 months. Oral samples were also collected by rubbing disposable medical sterile swabs on the buccal mucosa. Routine blood tests and biochemical indicators were measured using the fully automated biochemical analyzer. Oral microbial composition of oral samples were determined using whole-genome metagenomic analysis in all participants. Correlations were analyzed between the oral microbiota and blood lipids.

RESULTS

Study enrollment included 14 participants, 7 healthy controls and 7 patients with severe OSA. At the species level, the relative abundances of Prevotella, Alloprevotella, Bacteroides, Veillonella_tobetsuensis, Candidatus saccharimonas, and Leptotrichia in the groups with severe OSA were significantly lower than those in the healthy controls (P both < 0.05). The abundances of Capnocytophaga, Veillonella, Bacillus_anthracis, Eikenella, and Kingella were significantly higher whereas the abundances of Gordonia and Streptococcus were significantly lower in the group with severe OSA compared to the severe OSA-CPAP group (P < 0.05 for both). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), 4 pathways changed in the group with severe OSA compared with healthy controls (P both < 0.05). Pathways related to Novobiocin biosynthesis, 2-Oxocarboxylic acid metabolism, and Histidine metabolism were enriched in the patients with severe OSA. Nine pathways showed significant differences with regard to the relative abundances of phenylalanine metabolism; alanine, aspartate, and glutamate metabolism; one carbon pool by folate; monobactam biosynthesis; 2-oxocarboxylic acid metabolism; arginine biosynthesis and vitamin B6 metabolism; novobiocin biosynthesis; and arginine and proline metabolism, which were significantly higher in the group with severe OSA compared to the severe OSA-CPAP group (P both < 0.05). The Spearman correlation analysis between blood lipid parameters and oral microbiota components showed that negative correlations were observed between total cholesterol and Streptomyces (r =  - 0.893, P = 0.007), and high-density lipoprotein cholesterol (HDL-C) and Gordonia (r = - 0.821, P = 0.023); positive correlations were observed between HDL-C and Candidatus saccharimonas (r = 0.929, P = 0.003), and low-density lipoprotein cholesterol (LDL-C) and Capnocytophaga (r = 0.893, P = 0.007).

CONCLUSION

There was an apparent discrepancy of the oral microbiota and metabolic pathways between the group with severe OSA and controls, and CPAP significantly changed oral microbial abundance and metabolic pathways in patients with severe OSA. Correlation analysis showed that these oral bacteria were strongly correlated with the blood lipids level.

摘要

目的

口腔微生物群与全身健康密切相关,但很少有研究调查阻塞性睡眠呼吸暂停(OSA)患者的口腔微生物群。本研究旨在确定重度OSA患者口腔微生物群的变化,以及持续气道正压通气(CPAP)治疗后口腔微生物群的变化。

方法

2020年11月至2021年8月招募研究参与者。收集健康对照者、重度OSA患者以及接受CPAP治疗3个月后的重度OSA患者的全夜多导睡眠图(PSG)睡眠参数。还通过将一次性医用无菌拭子在颊黏膜上擦拭来收集口腔样本。使用全自动生化分析仪测量常规血液检查和生化指标。对所有参与者的口腔样本进行全基因组宏基因组分析以确定口腔微生物组成。分析口腔微生物群与血脂之间的相关性。

结果

研究共纳入14名参与者,7名健康对照者和7名重度OSA患者。在物种水平上,重度OSA组中普雷沃菌属、嗜胨菌属、拟杆菌属、户田韦荣球菌、假诺卡氏糖单胞菌属和纤毛菌属的相对丰度显著低于健康对照组(P均<0.05)。与重度OSA - CPAP组相比,重度OSA组中二氧化碳嗜纤维菌属、韦荣球菌属、炭疽芽孢杆菌、艾肯菌属和金氏菌属的丰度显著更高,而戈登菌属和链球菌属的丰度显著更低(两者P<0.05)。根据京都基因与基因组百科全书(KEGG),与健康对照组相比,重度OSA组中有4条通路发生了变化(P均<0.05)。与新生霉素生物合成、2 - 氧代羧酸代谢和组氨酸代谢相关的通路在重度OSA患者中富集。九条通路在苯丙氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢、叶酸一碳池、单环β - 内酰胺生物合成、2 - 氧代羧酸代谢、精氨酸生物合成和维生素B6代谢、新生霉素生物合成以及精氨酸和脯氨酸代谢的相对丰度方面存在显著差异,与重度OSA - CPAP组相比,重度OSA组中这些通路显著更高(两者P<0.05)。血脂参数与口腔微生物群成分之间的Spearman相关性分析表明,总胆固醇与链霉菌属之间呈负相关(r = - 0.893,P = 0.007),高密度脂蛋白胆固醇(HDL - C)与戈登菌属之间呈负相关(r = - 0.821,P = 0.023);HDL - C与假诺卡氏糖单胞菌属之间呈正相关(r = 0.929,P = 0.003),低密度脂蛋白胆固醇(LDL - C)与二氧化碳嗜纤维菌属之间呈正相关(r = 0.893,P = 0.007)。

结论

重度OSA组与对照组之间口腔微生物群和代谢通路存在明显差异,CPAP显著改变了重度OSA患者的口腔微生物丰度和代谢通路。相关性分析表明这些口腔细菌与血脂水平密切相关。

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