Infant Growth and Microbiome Study 2

婴儿生长和微生物组研究 2

基本信息

批准号：
9769010
负责人：
GARY D. WU
金额：
$ 70.02万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-28 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9769010
关键词：
16S ribosomal RNA sequencing 2 year old Address Adult African American Age Age-Months Animal Model Animals Antibiotics Appetite Regulation Behavioral Biological Markers Birth Breast Feeding Child Childhood Clinical Data Data Set Desire for food Development Diet Dyslipidemias Enrollment Epidemiology Evaluable Disease Feces Feeding Patterns Food Funding Future Genetic Predisposition to Disease Growth Health Health Personnel Hormonal Hormones Human Hypertension Infant Infant Development Intervention Knowledge Length Life Link Longitudinal prospective study Mediation Metabolic Metabolism Modeling Non-Insulin-Dependent Diabetes Mellitus Not Hispanic or Latino Obesity Outcome Pattern Physiological Plasma Population Prevention Measures Process Prospective cohort study Public Health Resistance Risk Factors Role Sampling Socioeconomic Status Sucking Behavior Taxonomy Time Weight Weight Gain Woman age group design directed attention epidemiology study feeding gestational weight gain gut bacteria gut microbiome gut microbiota healthy weight high dimensionality high risk increased appetite infancy insight maternal stress metabolome metabolomics microbiome microbiome research microbiota modifiable risk obesity development obesity in children obesity prevention obesity risk pregnant prevent programs prospective public health relevance sucking synergism

项目摘要

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.

描述（由申请人提供）：肥胖是一个重大的全国性健康问题，在美国，大约 10% 的两岁以下儿童的身高体重超过 95%。对于 2 至 5 岁的非裔美国儿童，19% 的非裔美国儿童肥胖（BMI > 95%）。生命中的 6 个月与童年后期的肥胖有关，因此婴儿期可能是预防肥胖的关键窗口，因为与医疗保健提供者的频繁接触、父母对预防婴儿饮食的控制以及未来措施的其他优势。可能性然而，为了制定预防婴儿期体重快速增加的公共卫生策略，必须充分了解母亲体重指数、妊娠期体重增加、分娩方式、抗生素暴露、婴儿模式。体重增加、喂养方式、母亲压力、社会经济地位、人群血统和遗传倾向与儿童肥胖风险相关，但它们的作用机制、协同作用和相对重要性仍不清楚。最近的动物模型研究证明了因果关系。关系之间的关系在儿童和成人中，肠道微生物群的改变与肥胖有关，并且已经记录了微生物群对食欲调节的间接影响。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龄阶段体重过度增加之间的联系。这是一项针对出生至 24 个月的儿童的前瞻性纵向研究，我们将招募非裔美国孕妇及其健康的女性。我们将收集流行病学（母亲 BMI、妊娠体重增加、分娩方式、生长轨迹、抗生素暴露）、行为（吸吮行为、喂养方式、饮食）和足月婴儿的样本，以获取 300 名 24 个月大的可评估婴儿的样本。已知与儿童肥胖相关的激素（食欲和代谢调节）参数，以及用于分析肠道微生物群和血浆代谢组的粪便和血浆我们将使用中介分析来整合已知的数据。我们认为，早期摄入食物和非推荐类型的补充食品与肠道微生物群的改变有关。代谢组和激素环境，导致婴儿期体重早期快速增加，并在 2 岁时体重增加过多。这些发现将为影响儿童肥胖的因素提供新的见解，并将有助于产生假设。进行更多的机制研究，并且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。