DiGiulio Daniel B, Callahan Benjamin J, McMurdie Paul J, Costello Elizabeth K, Lyell Deirdre J, Robaczewska Anna, Sun Christine L, Goltsman Daniela S A, Wong Ronald J, Shaw Gary, Stevenson David K, Holmes Susan P, Relman David A
March of Dimes Prematurity Research Center, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304;
March of Dimes Prematurity Research Center, Stanford University School of Medicine, Stanford, CA 94305; Department of Statistics, Stanford University, Stanford, CA 94305;
Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):11060-5. doi: 10.1073/pnas.1502875112. Epub 2015 Aug 17.
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.
尽管人类微生物群在健康中起着关键作用,但我们对孕期及产后微生物群组成动态的了解并不完整。我们对49名孕妇进行了一项病例对照研究,其中15人早产。我们从这些女性中的40人身上,分析了在妊娠期每周前瞻性收集以及产后每月从阴道、远端肠道、唾液和牙齿/牙龈收集的3767份标本的细菌分类组成。使用线性混合效应模型、基于类中位数的聚类分析和马尔可夫链模型来分析群落的时间趋势、群落结构和阴道群落状态转变。孕期所有四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(随时间变化趋势的P>0.05)。阴道群落状态类型中乳酸菌含量低的类型(CST 4)的患病率与分娩时的孕周呈负相关(P = 0.0039)。对于CST 4且加德纳菌或脲原体丰度升高的受试者,早产风险更为明显。这一发现通过一组来自9名女性(其中4人早产)的246份阴道标本得到验证。大多数女性在产后经历了阴道群落紊乱,其特征是乳酸菌种类减少,而诸如嗜胨菌、普雷沃菌和厌氧球菌等多种厌氧菌增加。这种紊乱与分娩时的孕周无关,并持续长达1年。这些发现对于预测早产(一个主要的全球健康问题)以及理解产后持续改变的微生物群对母亲健康的潜在影响具有重要意义,包括短间隔妊娠后的妊娠结局。