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不同严重程度阻塞性睡眠呼吸暂停低通气患者肠道菌群特征初步分析

Preliminary analysis of intestinal microflora in patients with different severity of OSAHS

摘要目的:分析不同严重程度阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者肠道菌群多样性、丰度及结构组成等特征,并初步探讨其在OSAHS发生发展过程中的潜在作用。方法:纳入2018年12月至2019年9月山西医科大学第二医院体检中心的27名健康志愿者[男19例,女8例,年龄22~78(44.4±2.7)岁,简称N组]和山西医科大学第二医院睡眠医学中心确诊的100例OSAHS患者[男86例,女14例,年龄19~78(49.1±1.3)岁],收集相关睡眠监测数据及病史资料,根据睡眠呼吸暂停低通气指数(AHI)分级和有无并发症将OSAHS患者分为单纯轻度组(简称L组)、单纯中度组(简称M组)、单纯重度组(简称S组)和重度并发症组(简称Sc组),运用16S rRNA高通量测序技术对肠道菌群进行特征分析,生物信息学相关统计用QIIME2软件进行分析,临床资料采用SPSS 25.0软件统计分析。结果:各组间肠道菌群Alpha和Beta多样性差异无统计学意义( P>0.05)。门水平分析,OSAHS各组拟杆菌门菌群相对丰度较N组低(N:24.96%,L:18.31%,M:12.95%,S:15.78%,Sc:16.48%)。属水平分析,拟杆菌属(N组:16.03%,L组:10.82%,M组:9.79%,S组:9.29%,Sc组:8.25%)和粪杆菌属(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疾病严重程度呈负相关( r值分别为-0.887、-0.945)。而双歧杆菌属(N组:3.20%,L组:2.47%,M组:4.10%,S组:4.93%,Sc组:6.27%)和布劳特氏菌属(N组:2.52%,L组:3.59%,M组:3.81%,S组:4.11%,Sc组:5.86%)相对丰度与OSAHS疾病严重成正相关( r值分别为0.916、0.940)。与S组相比,Sc组的罗氏菌属(S组:10.22%,Sc组:6.65%)相对丰度降低,志贺菌属(S组:4.64%,Sc组:10.01%)相对丰度升高。冗余分析(RDA分析)示AHI、最低血氧饱和度(SpO 2min)、平均血氧饱和度(SpO 2mean)及最长呼吸暂停时间(Tmax)等指标与肠道菌群整体丰度差异无统计学意义( P>0.05),但不同菌属菌群丰度与睡眠监测各指标差异有统计学意义( P<0.05)。 结论:OSAHS患者存在肠道菌群紊乱,主要为产生短链脂肪酸的益生菌相对丰度降低和致病菌的增多,提示其可能与OSAHS的发生发展有关。

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abstractsObjective: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.Methods: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.Results:There was no significant difference in intestinal flora Alpha and Beta diversity among all groups ( P>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 (SpO 2min), The average saturation of blood oxygen (SpO 2mean) and The longest time of apnea (Tmax) were not significantly correlated with the overall abundance of intestinal flora ( P>0.05), However, there was a significant correlation between the abundance of different flora and sleep monitoring indicators. Conclusion: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.

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中华结核和呼吸杂志

中华结核和呼吸杂志

2021年44卷6期

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