The Development of Gut Microbiota and Behavioral Inhibition in Childhood: The Role of Early Stress and Brain Development

项目摘要 早期毒性应激可导致对神经发育和行为的长期影响 对儿童的影响。一种可能调节这些联系的机制是肠道 微生物组。有强有力的证据表明，肠道微生物区系的模式可能会影响 啮齿动物的神经发育和焦虑相关行为，但关于这方面的文献很少 人类的联想。我们研究团队的最新发现是第一个揭示 肠道微生物组显著预测1岁儿童的恐惧行为。因此，拟议的 这项研究将考察心理社会压力对肠道微生物区系发育的影响， 由慢性HPA轴激活以及HPA轴与HPA轴之间的双向关系所介导 在生命的头四年里形成微生物群和行为抑制。我们会 作为关系的中介者衡量这段时间内大脑发育的变化 微生物群和行为抑制之间的关系。在这一敏感时期，微生物群 和大脑发育迅速，可能最容易受到环境输入的影响。 参与者(n=200)将从NICHD资助的前瞻性纵向队列研究中抽取 (大脑和早期经验研究(BEE)；R01 HD091148-01A1)。将进行评估 在36个月和54个月时进行实验室访问，在6个月和24个月时进行家访。心理社会 压力将通过对负面育儿行为的观察性评估和 6个月和24个月时的家庭混乱和HPA轴的激活将通过头发皮质醇进行测量 在这些访问中。在所有年龄段，将收集粪便样本以评估微生物多样性和 成熟度和行为抑制将通过母体报告和观察来评估 测量。使用高分辨率磁共振成像的神经成像，扩散张量 成像和静息状态的fMRI将提供mPFC体积增长的测量和 海马体从15个月到54个月，以及结构和功能之间的连接 杏仁核和mPFC。最后，在54个月的时候，对少校进行了一次简短的结构化诊断访谈。 将进行儿童精神障碍(迷你国际神经精神病学访谈)。 这项研究将首次调查早期心理社会应激对肠道的影响。 微生物组、神经发育和焦虑相关行为。我们的长期目标是 确定肠道微生物群的定植对人脑发育及以后的影响 精神病理学的风险，以防止精神疾病的发生或减少其 严肃性。这项研究的发现，在儿童早期的敏感时期，将提供 可以在出生后不久为干预和预防工作提供信息的重要信息。

Project Summary Early toxic stress can lead to enduring long-term effects on neurodevelopment and behavioral outcomes in children. One mechanism that may mediate these associations is the gut microbiome. There is robust evidence that patterns of gut microbiota may influence neurodevelopment and anxiety-related behaviors in rodents, but there is sparse literature on this association in humans. Recent findings from our research team are the first to reveal that the gut microbiome significantly predicts fear behavior in 1-year-old children. Thus, the proposed study will examine the influence of psychosocial stress on the development of gut microbiota, mediated by chronic HPA axis activation, as well as the bidirectional relationship between the developing microbiome and behavioral inhibition across the first four years of life. We will measure alterations in brain development across this time as a mediator of the relationship between the microbiome and behavioral inhibition. During this sensitive period the microbiome and brain are rapidly developing and may be most susceptible to environmental input. Participants (n = 200) will be drawn from a prospective longitudinal cohort study funded by NICHD (Brain and Early Experience Study (BEE); R01 HD091148-01A1). Assessments will be conducted during lab visits at 36 and 54 months and home visits at 6 and 24 months of age. Psychosocial stress will be assessed via observational assessments of negative parenting behavior and household chaos at 6 and 24 months, and HPA axis activation will be measured via hair cortisol at these visits. At all ages, fecal samples will be collected to assess microbial diversity and maturity and behavioral inhibition will be assessed via maternal report and observational measurement. Neuroimaging using high resolution magnetic resonance imaging, diffusion tensor imaging, and resting state fMRI will provide measures of volumetric growth of the mPFC and hippocampus from 15 months to 54 months, and structural and functional connectivity between the amygdala and mPFC. Finally, at 54 mos a brief structured diagnostic interview for major pediatric psychiatric disorders will be conducted (Mini International Neuropsychiatric Interview). This study will be the first to investigate the influence of early psychosocial stress on the gut microbiome, neurodevelopment and anxiety related behavior. Our long-term goal is to determine how colonization of the gut microbiome impacts human brain development and later risk for psychopathology in order to prevent the onset of psychiatric illness or reduce its severity. Findings from this study, during a sensitive period of early childhood, will provide important information that could inform intervention and prevention efforts soon after birth.