Perinatal Precursors of Early Microbiome Development.

项目摘要 越来越多的证据表明，胎儿暴露于糖皮质激素可能会导致各种不良出生 结果。最近出现的关注胎儿的影响，产前皮质类固醇（AC） 为有早产风险的妇女提供预防性护理。虽然它们有效地减少了 某些新生儿发病的可能性，我们以前的研究发现， 处方的皮质类固醇在生命的第一个月内显著耗尽和不寻常的肠道微生物群， 与母亲没有接受这些药物的新生儿形成对比。我们还发现母亲的症状 抑郁症预测了婴儿肠道微生物群组成的显着变化，两者都更多 严重的抑郁症和更高水平的压力与更丰富的细菌物种有关， 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，他们的微生物组成有所不同。最后，我们的研究 表明母体阴道微生物组的细菌结构（新生儿微生物的关键来源） 微生物组）受到母体压力的影响。阴道内细菌群落改变的传播 分娩可能会破坏对健康至关重要的新生儿微生物环境。为了验证和扩展我们的 初步调查结果，我们建议确定：1）如果AC或母亲的情绪困扰在怀孕期间， 与不同的新生儿肠道微生物组相关，这些微生物组与母亲未接受 AC或没有痛苦，以及2）如果在出生时鉴定出不同的微生物基因和基因途径， 在生命早期持续或增加。我们的主要重点将是微生物物种， 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 阴道微生物组以及这些阴道微生物是否存在于新生儿肠道微生物组中。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，提供了阴道标本，并在怀孕的协变量措施。凳子 将从出生时和出生后1个月和3个月的婴儿中采集样品，沿着进一步的 测量母亲压力、抑郁症状和协变量。医疗记录将提供以下数据 AC以及将在分析中控制的其他协变量。多层次回归模型将是 用于检查目标，沿着弹性、网络和加权网络分析，以及综合 母体阴道和新生儿肠道数据集的宏基因组学和代谢组学分析。暴露于AC 母亲在怀孕期间的情绪困扰可能对婴儿的早期编程有影响， 微生物组和适应功能的未来中断，这对儿童的长期健康至关重要。结果可 阐明AC和孕产妇痛苦的微生物风险，风险的生物特征以及益生菌疗法的目标。

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.