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[阻塞性睡眠呼吸暂停低通气综合征不同严重程度患者肠道菌群的初步分析]

[Preliminary analysis of intestinal microflora in patients with different severity of OSAHS].

作者信息

Wang L J, Yang C, Dou Z J, Wang P P, Hu Z X, Wang B

机构信息

Department of Respiratory and Critical Care Medicine, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2021 Jun 12;44(6):543-549. doi: 10.3760/cma.j.cn112147-20201009-01027.

DOI:10.3760/cma.j.cn112147-20201009-01027
PMID:34102716
Abstract

To analyze the diversity, abundance and structural composition of intestinal microflora in patients with different severity of OSAHS, and to explore their potential role in the occurrence and development of OSAHS. A total of 27 healthy volunteers(N) [male 19, female 8, age 22-78(44.4±2.7)years old] of Health Examination Center of the Second Hospital of Shanxi Medical University and 100 patients with OSAHS [male 86, female 14, age 19-78(49.1±1.3) years old] of Sleep Medicine Center of the Second Hospital of Shanxi Medical University were enrolled from December 2018 to September 2019, and patient-related sleep monitoring data and medical history data were collected.According to the AHI classification and whether there were complications, OSAHS patients were divided into mild group (L), moderate group (M), severe group (S) and severe complication group (SC).Using 16S rRNA high-throughput sequencing technology to analyze the intestinal flora of all people, bioinformatics related statistics were analyzed by QIIME2 software, and clinical data were analyzed by SPSS 25.0 software. There was no significant difference in intestinal flora Alpha and Beta diversity among all groups (>0.05). At phylum level, the relative abundance of Bacteroides in OSAHS group was lower than that in normal group (N group: 24.96%, L group: 18.31%, M group: 12.95%, S group: 15.78%, Sc group: 16.48%). At genus level, the relative abundance of Bacteroides (N group:16.03%, L group: 10.82%, M group: 9.79%, S group: 9.29%, Sc group: 8.25%) and Faecalibacterium (N group: 11.21%, L group: 10.42%, M group: 10.21%, S group: 8.54%, Sc group: 6.27%) were negatively correlated with the severity of OSAHS (the values of r respectively were -0.887, -0.945) while the relative abundance of Bifidobacterium (N group: 3.20%, L group: 2.47%, M group: 4.10%, S group: 4.93%, Sc group: 6.27%) and Blautia (N group: 2.52%, L group: 3.59%, M group: 3.81%, S group: 4.11%, Sc group: 5.86%) were positively correlated with the severity of OSAHS (the values of r respectively were 0.916, 0.940) Compared with the S group, the relative abundance of Roseburia (S group: 10.22%, Sc group: 6.65%) in the Sc is lower and the relative abundance of Shigella(S group: 4.64%, Sc group: 10.01%) is higher. Redundancy analysis (RDA) showed that Apnea hypopnea index (AHI), The lowest oxygen saturation (SpOmin), The average saturation of blood oxygen (SpOmean) and The longest time of apnea (Tmax) were not significantly correlated with the overall abundance of intestinal flora (>0.05), However, there was a significant correlation between the abundance of different flora and sleep monitoring indicators. There is an intestinal microecological imbalance in patients with OSAHS, mainly due to the reduction of the relative abundance of probiotics producing short-chain fatty acids and the increase of pathogenic bacteria, suggesting that the disturbance of intestinal flora may be related to the occurrence and development of OSAHS.

摘要

分析不同严重程度阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者肠道微生物群的多样性、丰度和结构组成,并探讨其在OSAHS发生发展中的潜在作用。选取山西医科大学第二医院健康体检中心27名健康志愿者(N组)[男19例,女8例,年龄22 - 78(44.4±2.7)岁]和山西医科大学第二医院睡眠医学中心100例OSAHS患者[男86例,女14例,年龄19 - 78(49.1±1.3)岁],纳入时间为2018年12月至2019年9月,收集患者相关睡眠监测数据和病史资料。根据睡眠呼吸暂停低通气指数(AHI)分级及是否有并发症,将OSAHS患者分为轻度组(L组)、中度组(M组)、重度组(S组)和重度并发症组(SC组)。采用16S rRNA高通量测序技术分析所有人的肠道菌群,通过QIIME2软件进行生物信息学相关统计,用SPSS 25.0软件分析临床数据。各组肠道菌群的Alpha和Beta多样性差异无统计学意义(>0.05)。在门水平上,OSAHS组拟杆菌的相对丰度低于正常组(N组:24.96%,L组:18.31%,M组:12.95%,S组:15.78%,Sc组:16.48%)。在属水平上,拟杆菌(N组:16.03%,L组:10.82%,M组:9.79%,S组:9.29%,Sc组:8.25%)和粪杆菌(N组:11.21%,L组:10.42%,M组:10.21%,S组:8.54%,Sc组:6.27%)的相对丰度与OSAHS严重程度呈负相关(r值分别为 - 0.887、 - 0.945),而双歧杆菌(N组:3.20%,L组:2.47%,M组:4.10%,S组:4.93%,Sc组:6.27%)和布劳特氏菌(N组:2.52%,L组:3.59%,M组:3.81%,S组:4.11%,Sc组:5.86%)的相对丰度与OSAHS严重程度呈正相关(r值分别为0.916、0.940)。与S组相比,SC组中罗氏菌属(S组:10.22%,Sc组:6.65%)相对丰度较低,志贺氏菌属(S组:4.64%,Sc组:10.01%)相对丰度较高。冗余分析(RDA)显示,呼吸暂停低通气指数(AHI)、最低血氧饱和度(SpOmin)、平均血氧饱和度(SpOmean)和最长呼吸暂停时间(Tmax)与肠道菌群总体丰度无显著相关性(>0.05),但不同菌群丰度与睡眠监测指标存在显著相关性。OSAHS患者存在肠道微生态失衡,主要表现为产生短链脂肪酸的益生菌相对丰度降低,病原菌增加,提示肠道菌群紊乱可能与OSAHS的发生发展有关。

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