Perinatal Precursors of Early Microbiome Development.

项目摘要 越来越多的证据表明，胎儿接触糖皮质激素可能会导致各种不利的分娩。 结果。最近，人们开始关注产前使用皮质类固醇(AC)对胎儿的影响。 为有早产风险的妇女提供预防性护理。尽管它们有效地降低了 某些新生儿患病的可能性，我们之前的研究发现，母亲是 在出生的第一个月，处方中的皮质类固醇显著耗尽和不寻常的肠道微生物区系。 相比之下，母亲没有接受这些疫苗的新生儿。我们还发现，母亲的症状是 抑郁预示着婴儿肠道微生物区系组成的显著差异，两者都更多 严重的抑郁和更高的压力水平与更多的细菌物种有关， 调节类固醇的代谢。重要的是，性别差异也出现了。男婴的细菌分类群 与女孩相比，它们的微生物数量明显减少；微生物组成也不同。最后，我们的研究 表明产妇阴道微生物群(新生儿微生物的主要来源)的细菌结构 微生物群)受到母体压力的影响。细菌群落改变在阴道内的传播 分娩可能会扰乱对健康至关重要的新生儿微生物环境。验证和扩展我们的 初步发现，我们建议确定：1)AC或孕妇在怀孕期间的情绪困扰是否 与独特的新生儿肠道微生物群有关，这种微生物群不同于母亲没有接受过的新生儿 AC或没有痛苦，以及2)如果在出生时发现的不同的微生物基因和基因途径 在早期生活中持续或增加的。我们的主要关注点将是代谢的微生物种类 糖皮质激素。我们还将确定AC和情绪困扰是否与不同的母亲相关 阴道微生物群以及这些阴道微生物是否存在于新生儿肠道微生物群中。最后，我们 将在所有分析中检查胎儿/婴儿性别的调节作用。160名女性将完成 抑郁症状和压力，提供阴道标本，并在怀孕期间采取协变量措施。大便 样本将从出生时、出生后1个月和3个月的婴儿身上获得，并将进一步 测量母亲的压力、抑郁症状和协变量。医疗记录将提供关于 AC以及将在分析中控制的其他协变量。多水平回归建模将是 用于检查目标，以及弹性、净值和加权网络分析，以及综合分析 母体阴道和新生儿肠道数据集的元基因组学和代谢组学分析。暴露在空调中 怀孕期间的母亲情绪困扰可能会对婴儿的早期规划产生影响 微生物群和未来对儿童长期健康至关重要的适应功能的破坏。结果可以 阐明来自AC和产妇窘迫的微生物风险，风险的生物特征，以及益生菌治疗的目标。

Project Summary There is growing evidence that fetal exposure to glucocorticoids may contribute to a variety of adverse birth outcomes. Recent concern has emerged regarding the fetal effects of antenatal corticosteroids (AC) administered as preventive care to women who are at risk of preterm birth. Although they effectively reduce the likelihood of certain neonatal morbidities, our previous research found that neonates whose mothers were prescribed corticosteroids had significantly depleted and unusual gut microbiota in the first month of life, in contrast to neonates whose mothers did not receive them. We also found that a mother's symptoms of depression predicted a significant amount of variance in infant gut microbiota composition, with both more severe depression and higher levels of stress associated with a greater abundance of bacterial species that modulate metabolism of steroids. Importantly, sex differences also emerged. The bacterial taxa of male infants were significantly depleted in contrast to girls; and their microbial compositions differed. Lastly, our research indicates that bacterial structure of the maternal vaginal microbiome (a key source of microbes for the neonatal microbiome) is affected by maternal stress. Transmission of altered bacterial communities during vaginal delivery may disrupt neonatal microbial environments that are essential for health. To validate and extend our preliminary findings, we propose to determine: 1) if AC or maternal emotional distress in pregnancy are associated with a distinct neonatal gut microbiome that differs from neonates whose mothers did not receive AC or were not distressed, and 2) if distinct microbial genes and gene pathways identified at birth are sustained or increased through early life. Our primary focus will be on microbial species that metabolize glucocorticoids. We will also determine if AC and emotional distress are associated with a distinct maternal vaginal microbiome and whether these vaginal microbes are found in the neonatal gut microbiome. Finally, we will examine the moderating effect of fetal/infant sex in all analyses. 160 women will complete measures of depressive symptoms and stress, provide a vaginal specimen, and covariate measures in pregnancy. Stool samples will be acquired from infants at birth and at 1 month and 3 months postnatal, along with further measures of maternal stress, depressive symptoms and covariates. The medical record will provide data on AC as well as additional covariates that will be controlled for in analyses. Multilevel regression modeling will be used to examine the aims, along with elastic, net and weighted network analyses, in addition to integrated analyses of metagenomics and metabolomics for maternal vaginal and neonatal gut datasets. Exposure to AC and maternal emotional distress during pregnancy could have implications for early programming of the infant's microbiome and future disruption of adaptive function that is critical to the child's long term health. Results can clarify microbial risk from AC and maternal distress, bio-signatures of risk, and targets for probiotic therapies.