Infant Growth and Microbiome Study 2

 描述（由申请人提供）：肥胖是一个严重的国家健康问题，不放过任何年龄段。在美国，大约10%的两岁以下儿童的身高体重超过第95百分位数。儿童肥胖症对非裔美国儿童来说尤其令人担忧。到2至5岁时，19%的非洲裔美国儿童肥胖（BMI> 95百分位）。在出生后的前4到6个月内体重快速增加与儿童期的肥胖有关，因此婴儿期可能是预防肥胖的关键窗口。这一年龄范围对于未来的预防措施还有其他优势，因为与卫生保健提供者的频繁接触，父母对婴儿饮食的控制，以及 代谢程序可能发生在这个发育窗口期。然而，要制定公共卫生战略，以防止婴儿期体重迅速增加，必须充分了解因果因素。母亲BMI、妊娠期体重增加、分娩方式、抗生素暴露、婴儿体重增加模式、喂养习惯、母亲压力、社会经济地位、人口血统和遗传倾向与儿童肥胖风险相关，但其作用机制、协同作用和相对重要性仍不清楚。最近在动物模型中的研究表明，肠道细菌及其代谢产物与肥胖发展之间存在因果关系。在儿童和成人中，肠道微生物群的改变与肥胖有关，微生物群对食欲调节的间接影响也有牵连。已经记录了生命最初2年内肠道微生物群的变化。一个主要的知识差距是肠道微生物群及其代谢组的变化与这个年轻时期体重过度增加之间的联系。这是一项对出生至24个月的儿童进行的前瞻性纵向研究。我们将招募非裔美国孕妇及其健康足月婴儿，以获得300例24月龄可评价婴儿的样本。我们将收集已知与儿童肥胖相关的流行病学（母体BMI、妊娠期体重增加、分娩方式、生长轨迹、抗生素暴露）、行为（吸吮行为、喂养习惯、饮食）和激素（食欲和代谢调节）参数，以及粪便和血浆，以分析肠道微生物群和血浆代谢组。我们将使用中介分析来整合已知的流行病学风险因素，肠道微生物群，代谢组学和激素生物标志物，以确定潜在的机制和可改变的因素，这些因素是早期体重过度增加的基础。我们假设，早期引入食物和非推荐类型的辅食将与肠道微生物群、代谢组和激素环境的改变相关，导致婴儿期早期体重快速增加，到20岁时体重过度增加。这些发现将为影响儿童肥胖的因素提供新的见解，将有助于产生更多机制研究的假设，并可能在这一关键发育阶段制定有效的肥胖预防策略方面具有重要的临床实用性。

 DESCRIPTION (provided by applicant): Obesity is a significant national health problem that spares no age group. Approximately 10 percent of children less than two years of age in the U.S. have weight-for-length above the 95th percentile. Childhood obesity is particularly concerning for African American children. By ages 2 to 5 years, 19 percent of African American children are obese (BMI>95th percentile). Rapid weight gain in the first 4 to 6 months of life is associated with obesity later in childhood, so infancy may be a critical window for obesity prevention. This age range has other advantages for future prevention measures because of frequent contact with health care providers, parental control over infant diet, and the possibility that metabolic programming may occur in this developmental window. However, to develop public health strategies to prevent rapid weight gain in infancy, the causal factors must be well understood. Maternal BMI, gestational weight gain, birth delivery mode, antibiotic exposure, pattern of infant weight gain, feeding practices, maternal stress, socioeconomic status, population ancestry and genetic predisposition have been associated with childhood obesity risk, but their mechanisms of action, synergy, and relative importance remain unclear. Recent studies in animal models demonstrate cause-and-effect relationships between gut bacteria, their metabolites, and obesity development. In children and adults, alteration of gut microbiota is associated with obesity, and indirect effects of microbiota on appetite regulation have been implicated. Changes in gut microbiota in the first 2 years of life have been documented. A major knowledge gap is the link between changes in gut microbiota and its metabolome and excess weight gain during this young age. This is a prospective longitudinal study of children ages birth to 24 months. We will enroll pregnant African American women and their healthy, term infants, to achieve a sample of 300 evaluable infants at 24 months of age. We will collect epidemiological (maternal BMI, gestational weight gain, delivery mode, growth trajectory, antibiotic exposure), behavioral (sucking behavior, feeding practices, diet) and hormonal (appetite and metabolism regulating) parameters known to be associated with childhood obesity, as well as stool and plasma to analyze gut microbiota and the plasma metabolome. We will use mediation analysis to integrate known epidemiologic risk factors, intestinal microbiota, and metabolomic and hormonal biomarkers to identify potential mechanisms and modifiable factors underlying early excess weight gain. We hypothesize that early introduction of foods and non-recommended types of complementary foods will be associated with alterations in gut microbiota, the metabolome and hormonal milieu, resulting in early rapid weight gain in infancy and excess weight gain by age 2years. These findings will provide new insights into factors influencing childhood obesity, will serve to generate hypotheses for more mechanistic studies, and will likely have significant clinical utility in developing effective obesity prevention strateies in this critical developmental stage.