Maternal Stress and the Gut-Brain Axis in African American Infants

 描述(申请人提供)：与其他种族的婴儿相比，非裔美国人(AA)婴儿的母亲压力大、早产和生活贫困的可能性更大，而他们更不可能接受母乳喂养。这些差异转化为神经认知和社会情绪发育迟缓的更高风险。微生物区系-肠道-脑轴-通过神经、激素和免疫途径发挥作用-作为神经发育的重要贡献者正受到越来越多的关注。肠道微生物群在出生时由母亲的菌群建立，并根据分娩方式、胎龄和大小、喂养类型和抗生素暴露等围产期因素而变化。此后，饮食、疾病、疫苗接种和抗生素暴露进一步影响微生物组的发育。因此，在生命关键的头几年，出生前和出生后影响微生物组-肠道-脑轴的生物行为暴露可能会显著影响发育中的大脑。这项拟议的研究将调查肠道微生物组的组成是否与产前和出生后母亲应激有关，并在出生后18个月内对再生障碍性贫血婴儿的不良神经认知和社会情绪结果做出贡献。为了实现这一点，我们将利用我们正在进行的关于AA女性早产的纵向研究(R01NR014800)的生物行为数据，即登记了一组不同社会经济背景的˜800名AA孕妇，并在怀孕8-14周和24-30周时对她们进行跟踪调查。家长研究提供了有关产前母亲应激、心理神经免疫(PNI)功能障碍(如促炎和抗炎细胞因子、皮质醇)以及妊娠和分娩结局(如感染、抗生素、分娩方式、胎龄)的数据。对于出生的AA婴儿，从1周到18个月，拟议的研究将评估：(1)环境和遗传对肠道微生物组的影响；(2)婴儿肠道微生物组、PNI功能和神经认知和社会情绪发育之间的途径；以及(3)婴儿肠道微生物组、母亲照料和压力与婴儿神经认知和社会情绪发育之间的关联由于许多影响微生物组的因素是可改变的，因此通过实现我们的目标获得的知识具有促进下一代AA家庭健康的巨大潜力。这项研究的成功得到了代表微生物组、产科和母婴健康、遗传学、营养学、应激、流行病学和信息学专业知识的科学家的多学科合作的支持；拟议研究和家长研究的关键人员重叠；以及埃默里临床和翻译科学研究所(CTSA奖#NIH UL1TR000454)和基因组学核心实验室的支持。此外，亚特兰大是具有广泛社会经济地位的再生障碍性贫血妇女的家园，提供了再生障碍性贫血家庭的多样化样本，这使得研究中的生物行为因素有足够的变化，以区分它们对微生物组和婴儿神经认知和社会情感发育的独立和交互影响。

 DESCRIPTION (provided by applicant): Compared to infants of other races, African American (AA) infants are more likely to have mothers with high rates of stress, to be born preterm, and to reside in poverty, whereas they are less likely to be breastfed. These disparities translate into higher risks for neurocognitive and social-emotional developmental delays. The microbiota-gut-brain axis - which functions through neural, hormonal, and immunologic pathways - is receiving growing attention as an important contributor to neurodevelopment. The gut microbiome is established at birth from maternal flora and varies according to perinatal factors such as mode of delivery, gestational age and size, type of feeding, and antibiotic exposure. Thereafter, diet, illness, vaccination, and antibiotic exposures further influence microbiome development. Thus, prenatal and postnatal biobehavioral exposures that affect the microbiome-gut-brain axis in the critical first years of life may significantly impact the developing brain. The proposed research will investigate whether the composition of the gut microbiome associates with exposure to prenatal and postnatal maternal stress and contributes to adverse neurocognitive and social emotional outcomes for AA infants over the first 18-months of life. To accomplish this, we will leverage biobehavioral data from our on-going longitudinal study of preterm birth in AA women (R01 NR014800), that is enrolling a socioeconomically diverse cohort of ˜ 800 pregnant AA women and following them at 8-14 and 24-30 weeks' gestation through delivery. The parent study provides data on prenatal maternal stress, psychoneuroimmune (PNI) dysfunction (e.g., pro- and anti-inflammatory cytokines, cortisol) and pregnancy and birth outcomes (e.g., infections, antibiotics, delivery mode, gestational age). For the birthed AA infants, from 1-week through 18-months of age, the proposed study will evaluate: (1) Environmental and genetic influences on the gut microbiome; (2) The pathways between infant gut microbiome, PNI function, and neurocognitive and social-emotional development; and (3) The associations among the infant gut microbiome, maternal caregiving and stress, and infant neurocognitive and social-emotional development Because many factors that influence the microbiome are modifiable, the knowledge gained by achieving our Aims holds tremendous potential for promoting the health of the next generation of AA families. The success of this research is supported by our multidisciplinary collaboration of scientists representing expertise in the microbiome, obstetrics and maternal-child health, genetics, nutrition, stress, epidemiology and informatics; the overlap of key personnel for the proposed and parent studies; and support from Emory Clinical and Translational Science Institute (CTSA award # NIH UL1TR000454) and Genomics Core Laboratory. Also, Atlanta is home to AA women of broad socioeconomic status, providing a diverse sample of AA families, which allows for sufficient variation in the biobehavioral factors under study to distinguish their independent and interactive effects on the microbiome and infant neurocognitive and socio-emotional development.