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

• 批准号: 10673754
• 负责人: Rebecca Knickmeyer
• 金额: $ 70.62万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673754
• 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; Home visitation; Hormonal; Household; Human; Hydrocortisone; International; Intervention; Interview; Lactobacillus; Life; Literature; Long-Term Effects; Longitudinal Studies; Longitudinal cohort study; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mediating; Mediator; Mental disorders; Mission; Modeling; National Institute of Child Health and Human Development; National Institute of Mental Health; Neurosecretory Systems; Nursery Schools; Participant; Pattern; Performance; Predisposition; Prefrontal Cortex; Prevention; Problem behavior; Psychopathology; Psychophysiology; Psychosocial Influences; Psychosocial Stress; Public Health; Qualifying; Reporting; Research; Research Domain Criteria; Research Personnel; Resolution; Rest; Risk; Risk Factors; Rodent; Role; Sampling; School-Age Population; Schools; Severities; Source; Strategic Planning; Stress; Structure; Testing; Time; Veillonella; Visit; Work; aged; anxiety symptoms; anxiety-related behavior; bacterial community; 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

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.

项目摘要 早期毒性压力会导致对神经发育和行为的长期影响 儿童的结果。一种可能介导这些关联的机制是肠道 微生物组。有强有力的证据表明肠道菌群的模式可能会影响 啮齿动物中的神经发育和与焦虑相关的行为，但有关此的文献很少 人类协会。我们研究团队的最新发现是第一个揭示 肠道微生物组可以显着预测1岁儿童的恐惧行为。因此，提议 研究将检查社会心理压力对肠道菌群发展的影响， 由慢性HPA轴激活以及双向关系 在生命的头四年中，发展微生物组和行为抑制作用。我们将 作为这种关系的调解人，衡量大脑发育的改变 在微生物组和行为抑制之间。在这个敏感时期，微生物组 大脑正在迅速发展，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提取 （大脑和早期经验研究（BEE）； R01 HD091148-01A1）。评估将进行 在36和54个月的实验室访问期间，在6个月和24个月大时进行家庭访问。社会心理 将通过对负育儿行为的观察评估和 6个月和24个月的家庭混乱，HPA轴激活将通过头发皮质醇测量 在这些访问中。在各个年龄段中，都将收集粪便样品，以评估微生物多样性和 成熟度和行为抑制作用将通过母体报告和观察性评估 测量。使用高分辨率磁共振成像，扩散张量的神经影像学 成像和静止状态fMRI将提供MPFC和 海马从15个月到54个月，以及结构和功能连通性 杏仁核和MPFC。最后，在54 MOS上，简短的结构化诊断面试 将进行儿科精神疾病（迷你国际神经精神访谈）。 这项研究将是第一个研究早期社会心理压力对肠道的影响的研究 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殖如何影响人脑发育及以后 为了防止精神病发作或减少心理病理学的风险 严重程度。这项研究的发现，在童年的敏感时期，将提供 可以在出生后不久就可以为干预和预防工作提供信息的重要信息。