Perinatal Precursors of Early Microbiome Development.

早期微生物组发育的围产期前体。

基本信息

批准号：
10654730
负责人：
Susan Veronica Lynch
金额：
$ 67.08万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10654730
关键词：
Adrenal Cortex Hormones Adrenal Glands Affect Animal Model Atopobium vaginae Bacteria Birth Brain Caring Child Data Data Set Development Distress Elasticity Environment Epigenetic Process Exposure to Fetus Foundations Future Genes Glucocorticoids Health Human Hydrocortisone Hypothalamic structure Infant Life Measures Medical Records Mental Depression Mental Health Metabolic Metagenomics Microbe Modeling Mothers Neonatal Newborn Infant Pathway Analysis Pathway interactions Perinatal Pituitary Gland Play Pregnancy Premature Birth Preventive care Process Research Research Support Risk Sex Differences Source Specimen Steroids Stress Structure Symptoms System Time Vagina Vaginal delivery procedure Vertical Transmission Woman adverse birth outcomes antenatal bacterial community biological adaptation to stress biosignature boys depressive symptoms emotional distress emotional symptom fetal gastrointestinal girls gut microbiome gut microbiota hypothalamic-pituitary-adrenal axis infant gut microbiome lung development male maternal depression maternal stress metabolomics microbial microbial composition microbiome microbiota neonatal morbidity neonate offspring physical conditioning postnatal prenatal exposure probiotic therapy response risk/benefit ratio sex standard of care steroid metabolism stool sample stressor transmission process vaginal microbiome

项目摘要

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.

项目概要越来越多的证据表明，胎儿接触糖皮质激素可能导致多种不良分娩结果。最近人们开始关注产前皮质类固醇 (AC) 对胎儿的影响对有早产风险的妇女进行预防性护理。虽然它们有效地减少了某些新生儿发病的可能性，我们之前的研究发现，母亲患有以下疾病的新生儿处方皮质类固醇在生命的第一个月内显着耗尽且异常的肠道微生物群，与母亲没有接受的新生儿形成鲜明对比。我们还发现，妈妈的症状抑郁症预示着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的压力水平与更丰富的细菌种类有关调节类固醇的代谢。重要的是，性别差异也出现了。男性婴儿的细菌分类群与女孩相比，她们的精力明显减少；并且它们的微生物组成也不同。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）受到母亲压力的影响。阴道期间改变的细菌群落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根据初步调查结果，我们建议确定：1）妊娠期 AC 或母亲情绪困扰是否是与独特的新生儿肠道微生物组有关，该微生物组与母亲未接受过治疗的新生儿不同 AC 或没有感到痛苦，以及 2) 出生时确定的不同微生物基因和基因途径是否在生命早期持续或增加。我们的主要关注点是代谢的微生物物种糖皮质激素。我们还将确定 AC 和情绪困扰是否与独特的母亲相关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 名女性将完成以下措施抑郁症状和压力，提供阴道标本，以及妊娠期的协变量测量。凳子将从婴儿出生时以及产后 1 个月和 3 个月采集样本，并进一步采集母亲压力、抑郁症状和协变量的测量。病历将提供以下数据： AC 以及将在分析中控制的其他协变量。多级回归模型将除了综合分析之外，还用于检查目标以及弹性、净值和加权网络分析对孕产妇阴道和新生儿肠道数据集进行宏基因组学和代谢组学分析。接触交流电怀孕期间母亲的情绪困扰可能会对婴儿的早期规划产生影响微生物组和未来适应功能的破坏对儿童的长期健康至关重要。结果可以阐明 AC 和孕产妇痛苦带来的微生物风险、风险的生物特征以及益生菌治疗的目标。