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

肠道菌群的发育和儿童时期的行为抑制：早期压力和大脑发育的作用

基本信息

批准号：
10266177
负责人：
Rebecca Knickmeyer
金额：
$ 71.49万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
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：
2020-09-18 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10266177
关键词：
1 year old Address Adult Age Age-Months Amygdaloid structure Animals Anxiety Anxiety Disorders Behavior Behavioral Behavioral inhibition Bifidobacterium Biochemical Biological Markers Birth Brain Child Child Rearing Childhood Chronic Development Diagnosis Diagnostic Diffusion Magnetic Resonance Imaging Dimensions Early Intervention Exposure to Family Fright Functional Magnetic Resonance Imaging Funding Goals Growth Hair Health Resources Hippocampus (Brain)Home visitation Hormonal Household Human Hydrocortisone International Intervention Interview Lactobacillus Lead Life Literature Long-Term Effects Longitudinal Studies Longitudinal cohort study Magnetic Resonance Imaging Measurement Measures Medial Mediating Mediator of activation protein Mental disorders Mission Modeling National Institute of Child Health and Human Development National Institute of Mental Health Neurosecretory Systems Nursery Schools Participant Pattern Performance Prefrontal Cortex Prevention Problem behavior Psychopathology Psychophysiology Psychosocial Influences Psychosocial Stress Public Health Reporting Research Research Domain Criteria Research Personnel Resolution Rest Risk Risk Factors Rodent Role Sampling Schools Severities Source Strategic Planning Stress Structure Testing Time Veillonella Visit Work aged anxiety symptoms anxiety-related behavior bacterial community base behavioral outcome biopsychosocial brain behavior brain pathway caregiving clinically significant cohort early childhood early experience environmental stressor experience gut colonization gut microbiome gut microbiota gut-brain axis high risk high risk population hypothalamic-pituitary-adrenal axis infancy maternal separation microbial microbial colonization microbial community microbiome microbiome analysis microbiota neural circuit neurodevelopment neuroimaging neuropsychiatry novel prevent preventive intervention prospective psychosocial response social relationships social situation substance use

项目摘要

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.

项目概要早期的毒性应激可能会对神经发育和行为产生持久的长期影响儿童的结果。可能介导这些关联的一种机制是肠道微生物组。有强有力的证据表明肠道微生物群的模式可能会影响啮齿类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中的关联。我们的研究团队最近的研究结果首次揭示了肠道微生物群可以显着预测 1 岁儿童的恐惧行为。因此，建议的研究将检查社会心理压力对肠道微生物群发展的影响，由慢性 HPA 轴激活介导，以及在生命的前四年中发展微生物组和行为抑制。我们将测量这段时间内大脑发育的变化作为关系的中介微生物组和行为抑制之间的关系。在这个敏感时期，微生物组大脑正在快速发育，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 个月大时进行实验室检查，以及在 6 个月和 24 个月大时进行家访。社会心理将通过对消极养育行为的观察评估来评估压力 6 个月和 24 个月时家庭混乱，HPA 轴激活将通过头发皮质醇测量在这些访问中。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亲报告和观察进行评估测量。使用高分辨率磁共振成像、扩散张量进行神经成像成像和静息态功能磁共振成像将提供 mPFC 和 15个月至54个月期间的海马体，以及海马体之间的结构和功能连接杏仁核和 mPFC。最后，在 54 个月时，对专业进行了简短的结构化诊断访谈将进行儿科精神疾病（小型国际神经精神病学访谈）。这项研究将首次调查早期社会心理压力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组的定植如何影响人类大脑发育以及随后的研究精神病理学风险，以预防精神疾病的发作或减少其发生严重程度。这项研究的结果将在幼儿期的敏感时期提供可以为出生后不久的干预和预防工作提供信息的重要信息。