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 虽然肥胖是对国民健康的严重威胁，但在预防方面却进展甚微。起步阶段 可能是防止其发展的适当时机，因为肥胖的轨迹越早停止， 产生负面健康后果的可能性就越小。早期肠道细菌群落的改变可能会影响 通过它们产生的代谢产物来控制后代肥胖。我们的总体工作因果模型是，前，后- 出生后的暴露会改变婴儿胃肠道中的微生物， 婴儿宿主可利用的胃肠代谢物，从而使婴儿一生的时间规划为 增加能量收获和脂肪沉积。我们的初步数据显示，母亲的BMI与 婴儿肠道微生物群组成，并且婴儿肠道微生物群组成 1个月大时的功能与2岁时的儿童肥胖状态相关，然而， 了解这些因素如何影响儿童的成长。虽然母亲的BMI是一个强大的 作为儿童BMI的决定因素，并不是所有孕前肥胖的妇女都会有孩子， 肥胖;对于体重正常的怀孕妇女来说，情况正好匡威。不同的生物机制 可能在依赖于产前环境的肥胖病因中很重要。因此，我们的总体假设将 在按孕妇怀孕前BMI类别分层的样本中进行测试。我们的目标将使用两个 目前在密歇根州建立并持续招募预期妊娠和分娩队列。我们预计 从每个队列（共600例）中招募300对配对，其中200对配对分别属于三种孕前BMI 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， 将不包括在内）。我们将获得妊娠期母体心脏代谢健康的数据（血糖， 血压水平），这可能有助于区分具有更“致病”体质的女性。产前 将测量尿代谢物以进一步表现代谢状态。抗菌剂暴露， 使用鸟枪宏基因组测序，通过抗菌素耐药基因丰度进行评估， 将衡量生物信息学方法以及病历摘要。此外，粪便代谢物 将在产前和产后进行评估，以确定肠道微生物群的可传播功能方面 在每个怀孕前BMI分层内。这些儿童将在1岁、2岁和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，这些研究将产生一个重要的多方面的成果。 三维“组学”数据集，将识别可能导致肥胖的微生物，代谢物和途径 在以后的生活中。这些可以作为未来干预措施的目标，以减轻肥胖的负担。我们的建议 提供证据和解决方案的能力，使公共卫生官员能够针对 每个BMI亚组根据独特的微生物和代谢组学相互作用提出具体建议 我们的结果显示。