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.

项目概要 尽管肥胖对国民健康构成严重威胁，但在婴儿期的预防方面却进展甚微。 可能是阻止其发展的好时机，因为越早停止肥胖的轨迹， 早期肠道细菌群落的改变产生负面健康后果的可能性就越小。 我们的总体工作因果模型是通过后代产生的代谢物来肥胖的。 产后接触会改变婴儿胃肠道中的微生物，进而改变 婴儿宿主可利用的胃肠道代谢物编程该婴儿一生 我们的初步数据显示，母亲的体重指数 (BMI) 与能量收获和脂肪沉积的增加有关。 1 个月大时婴儿肠道微生物群的组成，以及婴儿肠道微生物群的组成和 1 个月大时的功能与 2 岁时儿童肥胖状况相关，但我们的研究有限 尽管母亲体重指数是一个重要因素，但了解这些因素如何影响儿童生长。 BMI 是儿童 BMI 的决定因素，并非所有孕前肥胖的女性都会生出能够继续发育的孩子 肥胖；对于以正常体重进入妊娠期的女性则相反。不同的生物学机制不同。 肥胖的病因学可能很重要，取决于产前环境。因此，我们的总体假设将是。 在按母亲孕前 BMI 类别分层的样本中进行测试 我们的目标将使用两个来完成。 我们预计目前正在密歇根州建立并持续招募预期怀孕和出生队列。 从每个队列中招募 300 名双人组（总共 600 名），其中 3 个孕前 BMI 各有 200 名双人组 类别（正常体重、超重和肥胖；孕前体重不足在密歇根州和 将不包括在内）。我们将获得妊娠期母亲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”的产前体质的女性。 将测量尿液代谢物以进一步确定代谢状态的表型。 通过抗生素耐药性基因丰度进行评估，使用鸟枪法宏基因组测序和 将测量生物信息学方法以及病历摘要。 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 每个孕前 BMI 分层中的儿童将在 1、2 和 3 岁时接受身体尺寸评估。 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方面研究成果。 维度“组学”数据集将识别可能导致肥胖的微生物、代谢物和途径 我们的建议是，未来的干预措施可以针对这些目标，以减轻肥胖的负担。 提供证据和解决方案的能力，使公共卫生官员能够针对以下群体的成员 每个 BMI 亚组均根据独特的微生物和代谢组学相互作用提供具体建议 我们的结果揭示了这一点。