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

 描述(由申请人提供)：剖腹产(CS)分娩占美国新生儿总数的32%，与后代肥胖有关。人们对CS与肥胖风险之间的联系机制知之甚少。肠道微生物群因分娩方式的不同而不同，也与儿童肥胖症有关。在我们建立的种族和社会经济多元化出生队列(WHEALS；韦恩县健康、环境、过敏和哮喘纵向研究)中，早期肠道微生物群与2岁时的身体质量指数(BMI)类别相关；CS与明显的早期肠道微生物群相关，并与2岁时BMI增加相关；家中宠物的存在增加了微生物多样性，减少了CS与BMI之间的关联。我们的数据为肠道微生物群在CS-肥胖关系中的中介作用提供了证据。然而，要提供更有力的证据，还需要进行额外的研究。该项目建立在WHEALS的现有数据和对这些儿童的子集进行的数据收集的基础上，以检查肠道微生物群在CS-肥胖症关联中的作用。10-12岁的儿童将被邀请前往研究诊所进行全面的体型评估和抽血。使用16S rRNA和ITS2生物标记物基因和Illumina MiSeq平台，将在储存的早期(婴儿1个月和6个月)粪便样本以及这些儿童10-12岁的样本中测量肠道微生物组组成和预测功能。代谢组学分析将在这些粪便样本的子集中进行。肥胖将在2岁和10-12岁时被测量为BMI，从出生到10-12岁的BMI轨迹，以及10-12岁的人体测量、生物阻抗和炎症测量。加在一起，我们预计630名独特的儿童将接受为期10年的肥胖症测量和至少一项早期微生物组测量(405名儿童使用1个月的粪便样本，381名儿童使用6个月的粪便样本，其中包括300名儿童的1个月和6个月样本)。在这些儿童中，400人还将在10-12岁时进行肠道微生物群测量。我们的具体目标是：(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症有关；以及(3)检查肠道微生物组是否调节分娩方式与肥胖测量之间的关系。这种互补的“组学”方法从未被应用于儿童肥胖症的研究，可能会提供重要的见解。 纳入早期疾病发展以及适合干预的潜在目标。

 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.