基于16S rRNA测序技术分析妊娠期高血压疾病患者肠道菌群的变化  

Analysis of Intestinal Patients’Flora Changes with Pregnancy Induced Hypertension Based on 16S rRNA Sequencing Technology

作　　者：吴晶晶[1] 胡淋淋 黄凤凤[1] 赵梅晶[1] WU Jingjing;HU Linlin;HUANG Fengfeng;ZHAO Meijing(Department of Obstetrics,The Second Affiliated Hospital of Fujian Medical University,Quanzhou 362000,Quanzhou 362000,China)

机构地区：[1]福建医科大学附属第二医院妇产科,泉州362000

出　　处：《福建医科大学学报》2022年第6期545-551,共7页Journal of Fujian Medical University

基　　金：福建省自然科学基金项目(2019J01469)。

摘　　要：目的采用16S rRNA测序技术对妊娠期高血压疾病(PIH)患者肠道菌群的变化进行分析。方法选择2019年7月—2020年6月入住产科重症室的30例PIH孕妇作为研究对象,以同期住院分娩的30例正常妊娠孕妇作为对照组。采用前瞻性研究方法,收集2组患者的粪便标本,采用16S rRNA测序技术检测粪便菌群,并进行生物信息分析。结果(1)在PIH组和对照组中分别获得133350、128279个可用的序列。(2)肠道菌群α多样性分析显示,PIH组的Ace指数[811.21(567.58,1040.42)vs 1022.04(674.26,1269.09)]和Chao指数[811.97(551.00,1044.49)vs 1033.37(699.07,1285.37)]均较对照组显著下降,差别均有统计学意义(P<0.05);2组Shannon多样性指数(P=0.19)和Simpson多样性指数(P=0.87)差别均无统计学意义(P>0.05)。提示PIH组肠道菌群的丰度下降。(3)肠道菌群β多样性分析:采用主成分分析(PCA),基于加权UniFrac距离分析的主坐标分析PCoA图和非度量多维尺度(NMDS)估计β的多样性。从PC1和PC2评分中可看出2组间的分离,分别占总变异的8.12%和7.14%(P=0.029),NMDS分析表明,2组间菌群组成差别有统计学意义(拟合优度:R2=0.095,P=0.004)。(4)差异菌分析(门水平):在前10个菌门中,2组间只有候选糖杆菌门(TM7)的相对丰度存在显著差异。PIH组TM7丰度较对照组显著增加[0.0006(0.0001,0.0008)vs 0.0002(0.00004,0.0002),Z=-3.085,P=0.0037]。(5)差异菌分析(科、属水平),PIH组的肠道菌群中有益共生菌属(普雷沃菌属、毛螺菌属、巴恩斯氏菌属等)的比例较对照组丰度显著降低,而致病菌属(肠杆菌、放线菌、埃格特氏菌属等)的比例较对照组丰度显著增加,差别有统计学意义(P<0.05)。(6)采用LEfSe分析方法研究2组间的生物标志物,2组间有33个差异丰富的类群,其lgLDA评分均为>2。LEfSe分析显示,2组间的肠道菌群存在显著的细菌性差异。结论PIH患者肠道微生态失衡表现为菌群的丰度下降及菌群群落结构发生显�Objective Changes in the intestinal flora were analyzed by 16S rRNA sequencing.Methods A prospective observational research was conducted.We analyzed and compared the microbiota communities in the feces of 30 PIH patients admitted to department of obstetrics and intensive care of our hospital from July 2019 to June 2020,and pre-pregnancy body mass index-matched healthy controls using 16S rRNA gene sequencing.And performed the biological information analysis.Results(1)A total of 133350 available sequences were obtained in the PIH pregnancy group,and 128279 available sequences were obtained in the normal pregnancy group.(2)The A-diversity analysis of the gut flora showed that the ACE index and Chao index were significantly decreased in the PIH group compared with the normal pregnancy group(ACE index:811.21(567.58,1040.42)vs 1022.04(674.26,1269.09);Chao index:811.97(551.00,1044.49)vs 1033.37(699.07,1285.37),the difference was significant,P<0.05).The results of the Shannon diversity index(P=0.19)and the Simpson diversity index(P=0.87)were not significantly different.This suggests that the abundance of intestinal microflora decreased in the PIH group.(3)Intestinal flora diversity analysis:Principal component analysis(PCA),PCoA map and non-measured multi-dimensional scale(NMDS)to estimate the diversity.The separation between the two groups was seen from the PC1 and PC2 scores,accounting for 8.12%and 7.14%of the total variation,respectively(P=0.029<0.05).The NMDS analysis showed that there were significant differences in the microflora composition differences between the two groups(goodness of fit:R~2=0.095,P=0.004<0.01).(4)Analysis of phylum level bacteria showed:At the phylum level,the relative abundance of only the candidate saccharobacterium strain(TM7)differed significantly between the two groups out of the top 10 phyla.The PIH group had significantly increased TM7 abundance(0.0006(0.0001,0.0008)vs 0.0002(0.00004,0.0002)Z value-3.085,P=0.0037<0.01).(5)Analysis of family-and genus-level differential bacteria:The pro

关 键 词：妊娠高血压疾病 16S rRNA 肠道菌群 肠道微生态 菌群多样性 

分 类 号：R714.246[医药卫生—妇产科学]