Temporal and spatial variation of the human microbiota during pregnancy

Temporal and spatial variation of the human microbiota during pregnancy
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DOI:
10.1073/pnas.1502875112
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发表时间:
2015-09-01
影响因子:
11.1
通讯作者:
Relman, David A.
Relman, David A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DiGiulio, Daniel B.;Callahan, Benjamin J.;Relman, David A.

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尽管人类微生物群在健康中起着至关重要的作用,但我们对怀孕期间和怀孕后微生物群组成动态的了解尚不完整。我们对49名孕妇进行了病例对照研究,其中15人早产。从其中40名妇女中,我们分析了3767份标本的细菌分类组成,这些标本是在怀孕期间和分娩后每月从阴道、远端肠道、唾液和牙齿/牙龈中收集的。采用线性混合效应模型、基于媒介的聚类模型和马尔可夫链模型分析群落时间趋势、群落结构和阴道群落状态转变。在怀孕期间,4个身体部位的微生物群落分类组成和多样性保持显著稳定(随时间变化趋势P > 0.05)。乳酸菌缺乏阴道群落状态型(cst4)的患病率与分娩时胎龄呈负相关(P = 0.0039)。伴有加德纳菌或脲原体丰度升高的CST 4患者早产风险更明显。这一发现得到了来自9名妇女(其中4名早产)的246份阴道标本的验证。大多数妇女分娩后阴道菌群出现紊乱,其特征是乳酸杆菌种类减少,而各种厌氧菌如嗜胃杆菌、普雷沃氏菌和厌氧球菌种类增加。这种干扰与分娩时的胎龄无关,并持续长达1岁。这些发现对于预测早产(一个主要的全球健康问题)以及了解产后微生物群持续改变对孕产妇健康的潜在影响(包括妊娠间隔短后的妊娠结局)具有重要意义。
Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.