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.

项目摘要 在生命的前6个月，重量增长快速增长（RWG;> +0.67重量Z分数的变化）很强 早期生命和持续性肥胖和心脏代谢疾病的决定因素。肥胖影响美国的18.5％ 2-19岁的儿童，其中8.1％的<2岁儿童。虽然睡眠持续时间短，睡眠质量不佳 重要的早期危险因素，用于发展儿童对象，是国家预防的主要目标 努力，他们对早期RWG的影响知之甚少。婴儿期的睡眠效果模式，例如发育 在24小时的昼夜节律唤醒节奏中，重要的神经学里程碑可能对 影响RWG的风险。昼夜节律睡眠节奏的破坏与更大的肥胖有关 它的发展主要发生在生命的前6个月，与RWG相同的关键，​​预测时间范围。 在此期间，还建立了人类肠道微生物组（GM），以通过能量促进生长 收获和代谢信号传导。新兴数据表明睡眠可能会改变GM和婴儿代谢， 最终可能会影响对象。迄今为止，大多数GM研究都集中在 阴道与剖宫产分娩，抗生素使用和母乳喂养与以儿童肥胖为食的配方奶粉 风险。但是，证据限制了睡眠效果模式和GM发育是否相互作用以影响RWG。 扩大我们对早期肥胖风险中通用汽车作用的理解，包括建立睡眠 唤醒模式将提高我们在年轻时干预并防止肥胖症发作的能力。所以， 我们建议在12个月（3周，8周）和 3、6、9和12个月）的生活和评估婴儿睡眠效果模式和GM的大小和时机 发展为RWG的预测因素。该项目将实施一个新颖的概念框架 GM和睡眠效果模式是RWG的代谢贡献者。基本理论和分析 这项工作的框架将基于增长的生态模型（EMG），该模型侧重于儿童，母校， 家庭和环境因素有助于儿童的成长，并结合了人类的生态和 流行病学评估影响儿童健康结果的这些因素之间的更广泛的相互作用。 emg 在RWG上的睡眠和GM开发模型中，因素将作为协变量包括在内。我们的研究将解决 以下目的：1-调查婴儿睡眠效果模式与随后的RWG的关联6个月 使用时变效果模型在12个月时体重增加； 2-调查转基因开发的关联 RWG在6个月时，重量为12个月； 3-评估是否存在临时互动 婴儿睡眠效果模式和通用汽车的发展，以及这些关系是否影响RWG。项目发现将 告知未来的临床干预措施，包括睡眠和通用汽车方法，以降低婴儿期RWG的风险。 这种工作管道最终将导致制定基于证据的睡眠准则和通用汽车指南 通过鉴定RWG的关键发育时间间隔来防止肥胖以防止肥胖。