Infant Growth and Microbiome Study 2

 说明(申请人提供)：肥胖是一个严重的国民健康问题，没有一个年龄段的人可以幸免。在美国，大约10%的两岁以下儿童的身长体重超过了第95个百分位数。非裔美国儿童尤其关注儿童肥胖症。到2岁到5岁时，19%的非裔美国儿童患有肥胖症(BMI&GT；95%)。出生后4至6个月的体重快速增加与儿童后期肥胖有关，因此婴儿期可能是预防肥胖的关键窗口。这一年龄段对于未来的预防措施还有其他优势，因为经常与卫生保健提供者接触，父母对婴儿饮食的控制，以及可能 代谢编程可能发生在这个发育窗口。然而，要制定公共卫生战略以防止婴儿期体重迅速增加，必须充分了解原因。母亲体重指数、孕期体重增加、分娩方式、抗生素暴露、婴儿体重增加模式、喂养方式、母亲压力、社会经济地位、人口血统和遗传易感性与儿童肥胖风险有关，但它们的作用机制、协同作用和相对重要性尚不清楚。最近在动物模型中的研究表明，肠道细菌及其代谢物与肥胖发生之间存在因果关系。在儿童和成人中，肠道微生物区系的改变与肥胖有关，微生物区系对食欲调节的间接影响已被牵连。在生命的头两年里，肠道微生物区系的变化已经被记录在案。一个主要的知识缺口是肠道微生物区系及其代谢组的变化与年轻时体重增加过快之间的联系。这是一项对出生到24个月的儿童进行的前瞻性纵向研究。我们将招募怀孕的非洲裔美国妇女及其健康的足月婴儿，以实现对300名24个月大的可评估婴儿的抽样。我们将收集流行病学(母亲体重指数、孕期体重增加、分娩方式、生长轨迹、抗生素暴露)、行为(吮吸行为、喂养习惯、饮食)和荷尔蒙(食欲和新陈代谢调节)参数，以及粪便和血浆，以分析肠道微生物区系和血浆代谢组。我们将使用中介分析来整合已知的流行病学风险因素、肠道微生物区系以及代谢和激素生物标记物，以确定导致早期超重增加的潜在机制和可改变的因素。我们假设，早期引入食物和非推荐类型的补充食物将与肠道微生物区系、代谢物和激素环境的改变有关，从而导致婴儿早期快速体重增加和2岁时超重增加。这些发现将为影响儿童肥胖的因素提供新的见解，将有助于为更多的机械性研究提供假设，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价值。

 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.