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早/中孕期孕妇肠道菌群差异及其与妊娠期糖尿病的关系:前瞻性队列研究

王佩 马良坤 刘俊涛

王佩, 马良坤, 刘俊涛. 早/中孕期孕妇肠道菌群差异及其与妊娠期糖尿病的关系:前瞻性队列研究[J]. 协和医学杂志, 2021, 12(5): 721-728. doi: 10.12290/xhyxzz.20200122
引用本文: 王佩, 马良坤, 刘俊涛. 早/中孕期孕妇肠道菌群差异及其与妊娠期糖尿病的关系:前瞻性队列研究[J]. 协和医学杂志, 2021, 12(5): 721-728. doi: 10.12290/xhyxzz.20200122
WANG Pei, MA Liangkun, LIU Juntao. Difference in Gut Microbiota between the First and the Second Trimester of Pregnancy and the Association of Gut Microbiota with Gestational Diabetes Mellitus: A Prospective Cohort Study[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(5): 721-728. doi: 10.12290/xhyxzz.20200122
Citation: WANG Pei, MA Liangkun, LIU Juntao. Difference in Gut Microbiota between the First and the Second Trimester of Pregnancy and the Association of Gut Microbiota with Gestational Diabetes Mellitus: A Prospective Cohort Study[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(5): 721-728. doi: 10.12290/xhyxzz.20200122

早/中孕期孕妇肠道菌群差异及其与妊娠期糖尿病的关系:前瞻性队列研究

doi: 10.12290/xhyxzz.20200122
基金项目: 

中国医学科学院医学与健康科技创新工程 2016-I2M-1-008

详细信息
    通讯作者:

    刘俊涛  电话:010-69156230,E-mail: liujt@pumch.cn

  • 中图分类号: R714.256

Difference in Gut Microbiota between the First and the Second Trimester of Pregnancy and the Association of Gut Microbiota with Gestational Diabetes Mellitus: A Prospective Cohort Study

Funds: 

CAMS Innovation Fund for Medical Sciences 2016-I2M-1-008

More Information
    Corresponding author: LIU Juntao  Tel: 86-10-69156230, E-mail: liujt@pumch.cn
  • 摘要:   目的  探讨早/中孕期妇女的肠道菌群物种及功能特点,并分析其与妊娠期糖尿病(gestational diabetes mellitus, GDM)的关系。  方法  前瞻性收集并分析2017年5月至12月北京协和医院产科招募的早孕期孕妇的临床资料。依据孕24~28周75 g口服葡萄糖耐量试验(oral glucose tolerance test, OGTT)结果分为GDM组(研究组)和非GDM组(对照组)。分别于早孕期和中孕期收集两组孕妇粪便标本,对肠道菌群的16S rRNA V4可变区进行DNA测序及生物信息学分析。采用多因素Logistic回归分析探讨肠道菌群Alpha多样性及菌群相对丰度与GDM的关系。  结果  共145例符合纳入和排除标准的孕妇入选本研究。其中研究组34例、对照组111例。Alpha多样性分析显示,研究组早孕期Shannon指数和Simpson指数低于对照组(P均<0.05)。LEfSe分析显示,早孕期和中孕期,多个物种的相对丰度在两组间差异具有统计学意义(P均<0.05)。多因素Logistic回归分析显示,早孕期Shannon指数≤6.51(OR=3.15, 95% CI: 1.32~7.52)、Simpson指数≤0.96(OR=2.54,95% CI: 1.09~5.89)、拟普雷沃菌属(Alloprevotella)相对丰度≤0.004(OR=2.65, 95% CI: 1.09~6.44)、毛螺菌属(Lachnospira)相对丰度≤0.0107(OR=3.17, 95% CI: 1.33~7.55)是发生GDM的危险因素。肠道菌群功能预测比较显示, 早孕期时两组差异较少;中孕期时与能量代谢、糖代谢、氨基酸代谢和脂多糖(lipopolysaccharide, LPS)合成相关的通路在研究组显著富集。  结论  与健康孕妇相比,中孕期GDM患者肠道菌群的功能特点为LPS合成、能量代谢、糖代谢和氨基酸代谢相关通路显著富集; 早孕期肠道菌群物种多样性降低及某些菌属的丰度降低是发生GDM的危险因素。
    作者贡献:王佩负责研究设计、实施、数据采集、统计分析、撰写论文;马良坤指导研究设计;刘俊涛参与研究设计和实施、论文修改、经费支持。
    利益冲突:
  • 图  1  两组肠道菌群物种差异的LEfSe分析

    A.早孕期;B.中孕期

    图  2  两组肠道菌群功能通路相对丰度富集分析

    A.早孕期;B.中孕期

    表  1  两组孕妇的临床特征比较

    指标 研究组(n=34) 对照组(n=111) P
    年龄(x±s,岁) 35.5±4.3 32.3±3.9 <0.001
    经产妇[n(%)] 13(38.2) 24(21.6) 0.052
    孕前BMI(x±s,kg/m2) 22.8±3.8 21.9±2.6 0.187
    75 g OGTT(x±s,mmol/L)
        0 h血糖 4.9±0.4 4.5±0.2 <0.001
        1 h血糖 9.2±1.6 7.3±1.3 <0.001
        2 h血糖 8.3±1.3 6.4±0.9 <0.001
    GDM诊断孕周[M(P25, P75),周] 24.9(24.3,25.6) 24.7(24.1,25.4) 0.153
    早孕期留取标本孕周[M(P25, P75),周] 12.6(12.0,13.6) 12.7(12.1,13.4) 0.632
    中孕期留取标本孕周[M(P25, P75),周] 25.5(24.6,26.4) 25.5(24.4,26.7) 0.647
    BMI: 体质量指数;OGTT: 口服葡萄糖耐量试验;GDM: 妊娠期糖尿病
    下载: 导出CSV

    表  2  两组早孕期肠道菌群Alpha多样性比较及多因素Logistic回归分析

    Alpha多样性指数 研究组(n=34) 对照组(n=111) P 多因素Logistic回归分析*
    取值范围 OR(95% CI) P
    Chao1指数[M(P25, P75)] 918.9(749.4, 1450.7) 1082.3(857.1, 2037.1) 0.119 ≤1544.1 1
    >1544.1 0.49(0.19~1.27) 0.144
    Shannon指数(x±s) 6.19±0.93 6.60±0.84 0.019 ≤6.51 3.15(1.32~7.52) 0.009
    >6.51 1
    Simpson指数[M(P25, P75)] 0.96(0.94, 0.97) 0.97(0.95, 0.98) 0.004 ≤0.96 2.54(1.09~5.89) 0.030
    >0.96 1
    *多因素Logistic回归分析调整因素包括年龄和孕前体质量指数
    下载: 导出CSV

    表  3  早孕期肠道菌群主要物种与GDM关系的多因素Logistic回归分析结果

    菌属 取值范围 多因素Logistic回归分析*
    OR(95% CI) P R2
    拟普雷沃菌属 ≤0.004 2.65(1.09~6.44) 0.032 0.144
    >0.004 1
    毛螺菌属 ≤0.0107 3.17(1.33~7.55) 0.009 0.153
    >0.0107 1
    罗氏菌属 ≤0.0148 1
    >0.0148 2.06(0.83~5.13) 0.121 0.106
    巨单胞菌属 ≤0.001 33 1
    >0.001 33 2.75(0.94~8.04) 0.064 0.089
    GDM:同表 1*表 2
    下载: 导出CSV
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出版历程
  • 收稿日期:  2020-05-06
  • 录用日期:  2020-06-11
  • 网络出版日期:  2021-06-08
  • 刊出日期:  2021-10-12

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