Investigating the Influences of Sleep‐Wake Patterns and Gut Microbiome Development in Infancy on Rapid Weight Gain, an Early Risk Factor for Obesity

研究婴儿期睡眠-觉醒模式和肠道微生物组发育对体重快速增加的影响，体重快速增加是肥胖的早期危险因素

• 批准号: 9912021
• 负责人: Megan Elise Petrov
• 金额: $ 69.24万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9912021
• 关键词: 16S ribosomal RNA sequencing; 3 year old; Accounting; Address; Adult; Affect; Age; American; Americas; Antibiotics; Bacteroides fragilis; Bifidobacterium; Birth; Breast Feeding; Cesarean section; Characteristics; Child; Child Health; Clinical; Clinical Trials; Community Developments; Data; Development; Disease; Ecology; Environmental Risk Factor; Epidemiology; Evidence based practice; Exhibits; Family; Firmicutes; Future; Genus staphylococcus; Growth; Growth Factor; Harvest; Health; Home visitation; Homeostasis; Human; Infant; Intervention; Lead; Life; Longitudinal observational study; Low income; Mediator of activation protein; Metabolic; Metabolic Pathway; Metabolism; Modeling; Mothers; Neurologic; Obesity; Obesity Epidemic; Outcome; Pattern; Periodicity; Pregnancy; Prevention; Regulation; Risk; Risk Factors; Role; Route; Shapes; Signal Transduction; Sleep; Sleep disturbances; Staphylococcus aureus; Stimulus; Testing; Time; Vagina; Weight; Weight Gain; Work; World Health Organization; actigraphy; aged; base; beneficial microorganism; biobehavior; cardiometabolism; circadian; disorder risk; early childhood; ethnic diversity; evidence based guidelines; experience; feeding; gut microbiome; gut microbiota; improved; infancy; infant gut microbiome; mature animal; microbiome alteration; microbiome research; novel; obesity development; obesity in children; obesity prevention; obesity risk; pathogen; prenatal; prepregnancy; prevent; prospective; racial diversity; rapid infant weight gain; role model; sleep quality; therapy design; time interval; time use

PROJECT SUMMARY Rapid Weight Gain (RWG; >+0.67 change in weight-for-age Z-score) during the first 6 months of life is a strong determinant of early life and persistent obesity, and cardiometabolic diseases. Obesity affects 18.5% of American children aged 2-19 years and 8.1% of those <2 years. While short sleep duration and poor sleep quality are important early risk factors for the development of childhood obesity and are major targets of national prevention efforts, their impact on early RWG is less understood. Sleep-wake patterns in infancy, such as the development of the 24-hr circadian sleep-wake rhythm, an important neurological milestone, may be especially important for influencing risk of RWG. Disruptions to circadian sleep-wake rhythmicity are associated with greater adiposity and its development primarily occurs in the first 6 months of life, the same critical, predictive timeframe as RWG. The human gut microbiome (GM) is also established during this time to promote growth through energy harvesting and metabolic signaling. Emerging data suggest that sleep may alter the GM and infant metabolism, which ultimately may impact obesity. To date, most GM research has focused on the independent effects of vaginal vs. cesarean birth delivery, antibiotic use, and breastfeeding vs. formula feeding on childhood obesity risk. However, evidence is limited on if sleep-wake pattern and GM development interact to influence RWG. Broadening our understanding of the GM role in obesity risk in early life to include the establishment of sleep- wake patterns will improve our ability to intervene at a young age and prevent the onset of obesity. Therefore, we propose to prospectively follow 192 mother-infant pairs prenatally through 12 months (3 weeks, 8 weeks, and 3, 6, 9 and 12 months) of life and assess the magnitude and timing of infant sleep-wake patterns and GM development as predictors of RWG. This project will implement a novel conceptual framework that incorporates the GM and sleep-wake patterns as metabolic contributors for RWG. The underlying theoretical and analytical framework of this work will be based on the Ecological Model of Growth (EMG) that focuses on child, maternal, family, and environmental factors that contribute to a child’s growth and combines human ecology and epidemiology to evaluate broader interactions among these factors that influence child health outcomes. EMG factors will be included as covariates in models of sleep and GM development on RWG. Our study will address the following aims: 1- Investigate associations of infant sleep-wake patterns with subsequent RWG at 6 months and weight gain at 12 months using time-varying effect models; 2- Investigate associations of GM development with RWG at 6 months and weight at 12 months; and 3- Evaluate whether temporal interactions exist between infant sleep-wake patterns and GM development, and if these relations influence RWG. Project findings will inform future clinical interventions that include sleep and GM approaches to reduce the risk of RWG in infancy. This pipeline of work will ultimately lead to the development of evidence-based guidelines for sleep and GM development to prevent obesity through the identification of crucial developmental time intervals for RWG.

项目总结 在出生的前6个月内体重快速增加(RWG；&GT；+0.67按年龄计算的体重变化Z分数)是一种很强的 早期生活和持续性肥胖以及心脏代谢性疾病的决定因素。肥胖影响18.5%的美国人 2-19岁儿童，占2岁儿童的8.1%。而睡眠时间短和睡眠质量差 儿童肥胖发展的重要早期危险因素，是国家预防的主要目标 这些努力对早期RWG的影响还不是很清楚。婴儿期的睡眠-觉醒模式，如发育 24小时昼夜睡眠-觉醒节律，一个重要的神经学里程碑，可能对 影响RWG的风险。昼夜睡眠-觉醒节律性的紊乱与肥胖程度增加有关 它的发育主要发生在生命的前6个月，与RWG的关键和预测性时间框架相同。 人体肠道微生物组(GM)也是在此期间建立的，通过能量促进生长 收获和新陈代谢信号。新的数据表明，睡眠可能会改变GM和婴儿的新陈代谢， 这最终可能会影响肥胖。到目前为止，大多数转基因研究都集中在 阴道分娩与剖腹产、抗生素使用、母乳喂养与配方奶喂养对儿童肥胖的影响 风险。然而，关于睡眠-觉醒模式和GM发育是否相互作用影响RWG的证据有限。 扩大我们对GM在早期肥胖风险中的作用的理解，包括建立睡眠- 唤醒模式将提高我们在年轻时进行干预的能力，并防止肥胖的发生。因此， 我们建议前瞻性地跟踪192对母婴在产前12个月(3周、8周和 3个月、6个月、9个月和12个月)，评估婴儿睡眠-醒来模式和GM的大小和时间 发展作为RWG的预测指标。该项目将实施一个新的概念框架，其中包括 GM和睡眠-觉醒模式是RWG的代谢贡献者。基本的理论和分析 这项工作的框架将以生态增长模型(EMG)为基础，该模型侧重于儿童、母亲、 家庭和环境因素有助于儿童的成长，并结合了人类生态和 流行病学评估这些影响儿童健康结果的因素之间更广泛的相互作用。肌电 因素将作为协变量包括在RWG上的睡眠和GM发展模型中。我们的研究将解决 以下目标：1-调查婴儿睡眠-觉醒模式与随后6个月的RWG的关系 使用时变效应模型研究12个月时的体重增加；2-研究转基因发育的相关性 6个月的RWG和12个月的体重；以及3-评估 婴儿睡眠-觉醒模式和GM发育，以及这些关系是否影响RWG。项目调查结果将 告知未来的临床干预措施，包括睡眠和转基因方法，以降低婴儿期RWG的风险。 这一工作流水线最终将导致制定基于证据的睡眠和转基因指南 通过确定RWG的关键发育时间间隔来预防肥胖。