A Pre-, Peri-, and Post-natal Approach to Understanding the Risk and Mechanisms for Obesity

了解肥胖风险和机制的产前、围产期和产后方法

• 批准号: 10588373
• 负责人: Andrea E Cassidy-Bushrow
• 金额: $ 68.02万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588373
• 关键词: 2 year old; Acceleration; Adipose tissue; Affect; Age; Age Months; Antibiotics; Antimicrobial Resistance; Bacteria; Biochemical Pathway; Bioinformatics; Biological; Birth; Blood Glucose; Blood Pressure; Body Size; Body mass index; Categories; Child; Communities; Conceptions; Data; Data Set; Deposition; Development; Diet; Dimensions; Elderly; Energy Intake; Energy harvesting; Enrollment; Environment; Etiology; Exclusion; Feces; Future; Gastrointestinal tract structure; Gene Expression; Growth; Health; Infant; Intervention; Knowledge; Life; Measures; Medical Records; Meta-Analysis; Metabolic; Methods; Michigan; Microbe; Mothers; Obesity; Obesity Epidemic; Overweight; Pathogenicity; Pathway interactions; Perinatal; Phenotype; Pregnancy; Prevention; Public Health; Recommendation; Research; Risk; Risk Factors; Sampling; Shotguns; Subgroup; Testing; Time; Underweight; Weight; Weight Gain; Woman; antimicrobial; bacterial community; blood pressure elevation; cardiometabolism; causal model; cohort; combat; dietary; effective intervention; experimental study; falls; fasting blood glucose level; gastrointestinal; gut microbiota; infancy; maternal obesity; maternal weight; member; metabolic phenotype; metabolome; metabolomics; metagenomic sequencing; microbial; mother nutrition; obesity in children; obesity prevention; obesity risk; offspring; offspring obesity; postnatal; prenatal; prepregnancy; prepregnancy obesity; prevent; prospective; recruit; resistance gene; stool sample; unintended pregnancy; urinary

Project Summary Although obesity is a serious threat to the nation’s health, little progress has been made in its prevention. Infancy may be an opportune time to prevent its development since the sooner the trajectory towards obesity is halted, the less likely that negative health consequences will arise. Altered early gut bacterial communities may influence offspring obesity through the metabolites they produce. Our overarching working causal model is that pre-, peri- and postnatal exposures alter the microbes that colonize the infant’s gastrointestinal tract, which in turn alters the gastrointestinal metabolites available to the infant host thereby programming that infant for a lifetime of increased energy harvest and adipose deposition. Our preliminary data show that maternal BMI is associated with the infant gut microbiota composition at age 1 month, and that the infant gut microbiota composition and function at 1 month of age is associated with child obesity status at age 2 years, however we have limited knowledge on how these factors may causally influence child growth. Although maternal BMI is a strong determinant of child BMI, not all women with pre-pregnancy obesity will have children that will go on to develop obesity; the converse is true for women who enter pregnancy at normal weight. Different biological mechanisms may be important in the etiology of obesity dependent on prenatal environment. Thus, our overall hypothesis will be tested in a sample stratified by maternal pre-pregnancy BMI category. Our Aims will be completed using two currently established and continually enrolling prospective pregnancy and birth cohorts in Michigan. We expect to enroll 300 dyads from each cohort (600 total) with 200 dyads falling into each of three pre-pregnancy BMI categories (normal weight, overweight and obese; pre-pregnancy underweight is uncommon in Michigan and will not be included). We will obtain data on maternal cardiometabolic health in the pregnancy (blood glucose, blood pressure levels), which may help to differentiate women with a more “pathogenic” body habitus. Prenatal urinary metabolites will be measured to further phenotype the metabolic state. Antimicrobial exposures, assessed by antimicrobial resistance gene abundance, using shotgun metagenomic sequencing and bioinformatics methods, as well as medical record abstraction, will be measured. Additionally, stool metabolites will be assessed prenatally and postnatally to determine transmissible functional aspects of the gut microbiota within each pre-pregnancy BMI strata. The children will undergo body size assessment at ages 1, 2 and 3 years. The research proposed herein will be the first step in a continuum of studies that will generate an important multi- dimensional ‘-omics’ dataset which will identify microbes, metabolites, and pathways which may lead to obesity in later life. These can be targeted with future interventions to reduce the burden of obesity. Our proposal has the capacity to provide evidence and solutions which could allow public health officials to target members of each BMI sub-group with specific recommendations based on the unique microbial and metabolomic interactions that our results reveal.

项目摘要 尽管肥胖是对国家健康的严重威胁，但预防方面几乎没有取得进展。婴儿期 可能是防止其发展的机会，因为肥胖的轨迹越早， 负面健康后果的可能性越小。改变的早期肠道细菌群落可能会影响 后代肥胖通过它们产生的代谢产物。我们的总体工作因果模型是，前，周期 产后暴露改变了在婴儿的胃肠道中定居的微生物，从而改变了 婴儿宿主可用的胃肠道代谢物，从而对婴儿进行编程一生 增加能量收获和脂肪沉积。我们的初步数据表明材料BMI与 与婴儿肠道微生物群成分1个月，婴儿肠道菌群组成和 1个月大的功能与2岁的儿童肥胖状况有关，但是我们有限 了解这些因素如何有时会影响儿童成长。尽管Mater BMI是强大的 儿童BMI的决定因素，并非所有患有孕前肥胖的妇女都会有孩子会继续发展 肥胖;相反的是，以正常体重参加怀孕的妇女是正确的。不同的生物学机制 在肥胖的病因中可能很重要。那，我们的总体假设将 在通过母体孕前BMI类别分层的样品中进行测试。我们的目标将使用两个 我们预计目前在密歇根州建立并不断地招募了预期的怀孕和出生队列。 从每个队列（总共600个）中注册300个二元组，其中200个二元组落入了三个孕前BMI中的每一个 类别（正常体重，超重和肥胖；怀孕前体重不足在密歇根州并不常见 不会包括）。我们将获得有关孕妇孕妇心脏代谢健康的数据（血糖， 血压水平），这可能有助于使女性具有更“致病”的身体习惯。产前 将测量泌尿代谢物以进一步表型。抗菌暴露， 通过shot弹枪元基因组测序和 将测量生物信息学方法以及医疗记录抽象。另外，粪便代谢物 将通过产前和产后评估以确定肠道微生物群的可传播功能方面 在每个孕前BMI层中。孩子们将在1、2和3岁时接受体型评估。 本文提出的研究将是一系列研究的第一步，该研究将产生重要的多种多样 尺寸“ -omics”数据集，该数据集将识别可能导致肥胖症的微生物，代谢产物和途径 在以后的生活中。这些可以针对以后的干预措施来减少肥胖症的灼伤。我们的建议有 提供证据和解决方案的能力，可以允许公共卫生官员针对的成员 每个BMI子组具有基于独特的微生物和代谢组相互作用的特定建议 我们的结果揭示了。