Perinatal Precursors of Early Microbiome Development.

早期微生物组发育的围产期前体。

• 批准号: 10437940
• 负责人: Susan Veronica Lynch
• 金额: $ 67.21万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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/10437940
• 关键词: Adrenal Cortex Hormones; Adrenal Glands; Affect; Animal Model; Atopobium vaginae; Bacteria; Birth; Brain; Caring; Child; Data; Data Set; Development; Distress; Environment; Epigenetic Process; Exposure to; Fetus; Foundations; Future; Genes; Glucocorticoids; Health; Human; Hydrocortisone; Hypothalamic structure; Infant; Lead; 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 Disease Transmission; Woman; adverse birth outcomes; antenatal; bacterial community; biological adaptation to stress; 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

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多种不良出生 结果。最近对产前皮质类固醇（AC）的胎儿影响出现了关注。 对有早产风险的妇女进行预防护理。尽管它们有效地减少了 我们以前的研究发现，母亲是新生儿的可能性 处方的皮质类固醇在生命的第一个月中大大耗尽和不寻常的肠道菌群 与母亲没有收到的新生儿形成鲜明对比。我们还发现母亲的症状 抑郁症预测婴儿肠道菌群组成的差异很大，两者都更多 严重的抑郁症和更高水平的压力与大量的细菌物种相关 调节类固醇的代谢。重要的是，性别差异也出现了。雄性婴儿的细菌分类群 与女孩相反，被耗尽了。它们的微生物组成也有所不同。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）受母性压力的影响。阴道期间细菌群落改变的传播 分娩可能会破坏对健康必不可少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或孕妇情绪困扰是否在怀孕中 与独特的新生儿肠道微生物组相关，该肠道微生物组与母亲没有接受的新生儿不同 AC或不苦恼，2）如果出生时确定的不同的微生物基因和基因途径是 持续或增加早期。我们的主要重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有关 阴道微生物组以及这些阴道微生物是否在新生儿肠道微生物组中发现。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名妇女将完成措施 抑郁症状和压力，提供阴道标本和妊娠的协变量。凳子 样本将在出生时和产后1个月和3个月的婴儿中从婴儿中获取，并进一步 孕产妇压力，抑郁症状和协变量的度量。病历将提供有关 AC以及将在分析中控制的其他协变量。多级回归建模将是 用于检查目的以及弹性，净和加权网络分析的目的 对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 怀孕期间的母性情绪困扰可能会对婴儿的早期编程产生影响 微生物组和未来的自适应功能的破坏对孩子的长期健康至关重要。结果可以 阐明AC和母体困扰，风险的生物签名以及益生菌疗法的靶标的微生物风险。