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.

项目概要 出生后前 6 个月体重快速增加（RWG；年龄别体重 Z 值变化 >+0.67）是一个强有力的指标 早年和持续性肥胖以及心脏代谢疾病的决定因素。 18.5% 的美国人患有肥胖症 2-19 岁儿童，其中 2 岁以下儿童占 8.1%。虽然睡眠时间短、睡眠质量差 儿童肥胖发生的重要早期危险因素，是国家预防的主要目标 的努力，但它们对早期 RWG 的影响却鲜为人知。婴儿期的睡眠-觉醒模式，例如发育 24 小时昼夜节律的睡眠-觉醒节律是一个重要的神经学里程碑，对于 影响 RWG 的风险。昼夜节律性睡眠-觉醒节律紊乱与肥胖程度增加有关 它的发展主要发生在生命的前 6 个月，与 RWG 相同的关键、可预测的时间范围。 人类肠道微生物组（GM）也在这段时间建立，通过能量促进生长 收获和代谢信号。新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。迄今为止，大多数转基因研究都集中在独立影响上 阴道分娩与剖腹产、抗生素使用以及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 在生命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并预防肥胖发生的能力。所以， 我们建议对 192 对母婴进行产前 12 个月（3 周、8 周和 3、6、9 和 12 个月）并评估婴儿睡眠-觉醒模式和 GM 的程度和时间 发展作为 RWG 的预测因子。该项目将实施一个新颖的概念框架，其中包括 GM 和睡眠-觉醒模式作为 RWG 的代谢贡献者。基础理论和分析 这项工作的框架将基于生态增长模型（EMG），重点关注儿童、孕产妇、 家庭和环境因素有助于儿童的成长，并结合了人类生态学和 流行病学来评估影响儿童健康结果的这些因素之间更广泛的相互作用。肌电图 因素将作为协变量纳入 RWG 的睡眠和 GM 发育模型中。我们的研究将解决 目标如下： 1- 研究婴儿睡眠-觉醒模式与随后 6 个月时 RWG 的关联 使用时变效应模型计算 12 个月时的体重增加； 2- 调查转基因开发协会 6个月时的RWG和12个月时的体重； 3-评估之间是否存在时间相互作用 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 为未来的临床干预措施提供信息，包括睡眠和 GM 方法，以降低婴儿期 RWG 的风险。 这一工作流程最终将导致睡眠和 GM 循证指南的制定 通过确定 RWG 的关键发育时间间隔来预防肥胖。