Infant Growth and Microbiome Study 2

婴儿生长和微生物组研究 2

• 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
• 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; 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

 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（由适用提供）：肥胖是一个重大的国家健康问题，不避免年龄段。在美国，大约有10％的儿童的体重高于第95个百分位。儿童肥胖特别关注非裔美国儿童。到2至5岁的年龄，非洲裔美国儿童中有19％是肥胖的（BMI> 95％）。在生命的前4至6个月中，体重快速增加与童年后期的肥胖有关，因此婴儿期可能是预防肥胖症的关键窗口。由于与医疗保健提供者的频繁接触，对婴儿饮食的控制以及可能性，该年龄范围对于未来的预防措施还有其他优势 该代谢编程可能发生在此发展窗口中。但是，为了制定公共卫生策略以防止婴儿期快速增加体重，必须充分了解因果因素。产妇BMI，胎度体重增加，出生分娩模式，抗生素暴露，婴儿体重增加的模式，喂养实践，母校压力，社会经济状况，人口祖先和遗传倾向与儿童肥胖风险有关，但是它们的作用，协同，协同性和相对重要性仍然不清楚。动物模型的最新研究表明，肠道细菌，其代谢产物和肥胖发育之间的因果关系。在儿童和成人中，肠道微生物群的改变与肥胖有关，并且已经实施了微生物群对食欲调节的间接影响。肠道菌群的变化已记录在生命的头两年中。一个主要的知识差距是肠道微生物群的变化与其代谢组之间的联系与在这个年轻时超过体重增加之间的联系。这是对生日至24个月的儿童年龄的前瞻性纵向研究。我们将入学孕妇的非洲裔美国妇女及其健康的学期婴儿，以在24个月大时获得300名可评估婴儿的样本。我们将收集流行病学（母体BMI，妊娠体重增加，输送模式，生长轨迹，抗生素暴露），行为（吮吸行为，喂养实践，饮食）和马蹄铁（食欲和代谢调节）参数已知与儿童期观测值相关，以及stool and plasma以及PLASMA，以及PLASMA和PLASMASMA和PLASMA和PLAS MICROBSMA和PLAS MICTAMA和PLAS MICTAMA和PLASMA MEGSAMAMAMAMAMAMAMA和PLASMAMAME MEGAME和PLASMAMAME MIGASMA和PLASMAMAME MEGAME。我们将使用调解分析来整合已知的流行病学风险因素，肠道菌群以及代谢组和马匹生物标志物，以识别早期早期重量增长的潜在机制和可修改因素。我们假设早期引入食物和非备受推测的互补食品将与肠道微生物群，代谢组和马蹄铁的变化有关，从而导致婴儿期早期体重增加，并在2岁时提早体重增加。这些发现将为影响儿童对象的因素提供新的见解，有助于为更多的机械研究产生假设，并且在这个关键的发育阶段，可能会在制定有效的肥胖预防策略方面具有重要的临床实用性。