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

 描述（由申请人提供）：与其他种族的婴儿相比，非洲裔美国人（AA）婴儿更有可能有高压力率的母亲，早产，生活在贫困中，而他们不太可能被母乳喂养。这些差异转化为神经认知和社会情感发育迟缓的风险更高。微生物群-肠道-大脑轴-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在受到越来越多的关注。肠道微生物组在出生时从母体植物群建立，并根据围产期因素如分娩方式、胎龄和大小、喂养类型和抗生素暴露而变化。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，在生命的关键最初几年，影响微生物组-肠道-大脑轴的产前和产后生物行为暴露可能会显着影响发育中的大脑。拟议的研究将调查肠道微生物组的组成是否与产前和产后母体压力的暴露有关，并在出生后的前18个月内对AA婴儿的神经认知和社会情绪产生不良影响。为了实现这一目标，我们将利用我们正在进行的AA女性早产纵向研究（R 01 NR 014800）的生物行为数据，该研究招募了10800名AA孕妇的社会经济多样化队列，并在妊娠8-14周和24-30周至分娩期间对其进行随访。母体研究提供了产前母体压力、心理神经免疫（PNI）功能障碍（例如，促炎细胞因子和抗炎细胞因子，皮质醇）以及妊娠和分娩结果（例如，感染、抗生素、分娩方式、胎龄）。对于出生的AA婴儿，从1周到18个月大，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，神经认知和社会情感发育之间的途径;以及（3）婴儿肠道微生物组、母亲分娩和压力之间的关联，由于影响微生物组的许多因素是可以改变的，因此通过实现我们的目标所获得的知识对促进AA家庭下一代的健康具有巨大的潜力。这项研究的成功得到了我们代表微生物组，产科和母婴健康，遗传学，营养学，压力，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;拟议和父母研究的关键人员的重叠;以及埃默里临床和转化科学研究所（CTSA奖# NIH UL 1 TR 000454）和基因组学核心实验室的支持。此外，亚特兰大是家庭的AA妇女广泛的社会经济地位，提供了一个多样化的样本AA家庭，这使得足够的变化，在生物行为因素的研究，以区分其独立和互动的影响微生物组和婴儿神经认知和社会情感的发展。

 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.