Delivery mode, environment and the gut microbiome: influence on childhood body size

分娩方式、环境和肠道微生物组：对儿童体型的影响

• 批准号: 9187926
• 负责人: Andrea E Cassidy-Bushrow
• 金额: $ 60.47万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9187926
• 关键词: 2 year old; Age; Area; Asthma; Biological; Biological Markers; Birth; Blood; Body Size; Body fat; Body mass index; California; Categories; Cesarean section; Child; Childhood; Clinic Visits; County; Data; Data Collection; Desire for food; Development; Diet; Disease; Energy Intake; Environment; Epidemic; Equilibrium; Expenditure; Extrinsic asthma; Feces; Genes; Geographic Locations; Harvest; Health; Health system; Home environment; Human; Hypersensitivity; Individual; Infant; Inflammatory; Intervention; Laboratories; Life; Link; Longitudinal Studies; Longitudinal cohort study; Measures; Mediating; Metabolic; Obesity; Pathway interactions; Physical activity; Pregnancy; Pregnant Women; Prevalence; Public Health; Recruitment Activity; Research; Ribosomal RNA; Risk; Role; Sampling; San Francisco; Satiation; Signal Transduction; Universities; Vagina; Vaginal delivery procedure; base; cohort; early childhood; electric impedance; epidemiology study; follow-up; gut microbiome; infancy; insight; metabolic profile; metabolomics; microbial; microbiome; obesity in children; obesity risk; offspring; pet animal; public health relevance; socioeconomics; suburb; waist circumference

 DESCRIPTION (provided by applicant): Caesarean section (CS) delivery, which accounts for 32% of all US births, has been associated with offspring obesity. Little is known about the mechanisms linking CS with obesity risk. The gut microbiome, which varies by mode of delivery, is also associated with childhood obesity. In our established racially and socioeconomically diverse birth cohort (WHEALS; Wayne County Health, Environment, Allergy and Asthma Longitudinal Study), the early-life gut microbiome is associated with body mass index (BMI) category at age 2 years; CS is associated with both a distinct early-life gut microbiome and with increased BMI at age 2 years; and the presence of pets in the home, which increases microbial diversity, reduces the association between CS and BMI. Our data provide evidence for a mediating role of the gut microbiome in the CS-obesity relationship. However, to provide stronger evidence requires additional study. This project builds on extant data in WHEALS and on-going data collection in a subset of these children to examine the role of the gut microbiome in the CS-obesity association. Children will be invited for a research clinic visit for comprehensive body size assessment and blood draw at age 10-12 years. Gut microbiome composition and predicted function will be measured in banked early-life (1 and 6 months of infancy) stool samples and in samples from these children at age 10-12 years using the 16S rRNA and ITS2 biomarker genes and the Illumina MiSeq platform. A metabolomics analysis will be conducted in a subset of these stool samples. Adiposity will be measured as BMI at ages 2 and 10-12 years, BMI trajectory from birth to age 10-12 years, and anthropometric, bio-impedance and inflammatory measures at ages 10-12 years. Combined, we anticipate 630 unique children will have 10-year adiposity measures and at least one early-life microbiome measure (405 with 1 month and 381 with 6 month stool samples, which includes 300 children with paired 1 and 6 month samples). Of these children, 400 will also have gut microbiome measured at age 10-12 years. Our specific aims are to: (1) examine if mode of delivery is associated with childhood adiposity; (2) examine if the gut microbiome is associated with childhood adiposity; and (3) examine whether the gut microbiome mediates relationships between mode of delivery and measures of adiposity. Such a complementary "omics" approach has never been applied to the study of childhood obesity and is likely to provide critical insights into disease development in early-life as well as potential targets amenable for intervention.

 描述（由申请人提供）：剖腹产 (CS) 分娩占美国新生儿的 32%，但对于剖腹产与肥胖风险之间的关联机制知之甚少。在我们建立的种族和社会多样化出生队列（WHEALS；韦恩县健康、环境、过敏和哮喘纵向研究）中，生命早期肠道微生物组也与儿童肥胖有关。与 2 岁时的体重指数 (BMI) 类别相关；CS 与独特的早期肠道微生物组和 2 岁时体重指数的增加以及家中宠物的存在有关，这增加了微生物的多样性，我们的数据提供了肠道微生物组在 CS 与肥胖关系中的中介作用的证据，但是，为了提供更有力的证据，该项目需要基于 WHEALS 的现有数据和正在进行的数据。收藏对这些儿童的一个子集进行研究，以检查肠道微生物组在 CS-肥胖关联中的作用。儿童将被邀请参加研究诊所，以进行全面的身体尺寸评估和 10-12 岁时的肠道微生物组组成预测。将使用 16S rRNA 和 ITS2 生物标志物基因以及 Illumina 在储存的早期生命（婴儿 1 个月和 6 个月）粪便样本以及这些 10-12 岁儿童的样本中测量功能MiSeq 平台将对这些粪便样本的子集进行代谢组学分析，测量 2 岁和 10-12 岁时的 BMI、从出生到 10-12 岁的 BMI 轨迹以及人体测量、生物阻抗和体重。综合起来，我们预计 630 名独特的儿童将进行 10 年肥胖测量和至少一项生命早期微生物组测量。 （405 名儿童为 1 个月大的粪便样本，381 名儿童为 6 个月大的粪便样本，其中 300 名儿童为 1 个月大和 6 个月大的样本），其中 400 名儿童还将在 10-12 岁时进行肠道微生物组测量。 (1) 检查分娩方式是否与儿童肥胖有关；(2) 检查肠道微生物组是否与儿童肥胖有关；(3) 检查肠道微生物组是否介导这种关系；这种互补的“组学”方法从未应用于儿童肥胖的研究，并且可能提供重要的见解。 生命早期疾病的发展以及适合干预的潜在目标。