Gut Microbiome in Adults with Early Life Exposures to Environmental Chemicals

描述(由申请人提供)：关于发育和出生后接触环境化学品的微生物组的特征以及可能与糖代谢异常标记物的关联，将在&gt；500名年轻人中进行研究，他们是1986年至1987年在法罗群岛建立的一个独特的出生队列的成员，法罗群岛是一个接触环境化学品范围异常广泛的社区。队列成员将在28岁时被邀请进行临床检查，并将获得粪便样本。关于过去的化学暴露、饮食、病史和其他协变量的数据是在出生时和之前7、14和22岁的临床检查中获得的，队列中84%-90%的人(N=1,000)参与了这一研究。这些数据包括接触甲基汞、多氯联苯、滴滴涕和全氟化合物。临床检查将包括糖耐量试验。这些受试者的肠道微生物组的结构和功能将分两个阶段进行评估。每个样本中存在的微生物将通过16S rRNA基因测序确定，然后对选定的具有最大生物信息量的样本子集进行深层元基因组和后转录测序。与下游统计生物标记物的发现相结合，这将允许确定与早期生命化学暴露和随后的成人葡萄糖耐量相关的微生物分支、基因、途径或转录本。

DESCRIPTION (provided by applicant): The characteristics of the microbiome in regard to developmental and postnatal exposure to environmental chemicals and the possible associations with markers of glucose metabolism abnormalities will be examined in >500 young adults, who are members of a unique birth cohort established in 1986-1987 at the Faroe Islands, a community with an unusually wide range of exposures to environmental chemicals. Cohort members will be invited at age 28 years for clinical examination, and a fecal sample will be obtained. Data on past chemical exposures, diet, medical history and other covariates were obtained at birth and at previous clinical examinations at ages 7, 14, and 22 years, in which 84%-90% of the cohort (N = 1,000) participated. The data include exposures to methylmercury, PCBs, DDE, and perfluorinated compounds. The clinical examination will include glucose tolerance test. The structure and function of the gut microbiome of these subjects will be assessed in a two-stage process. The microbes present in every sample will be determined by 16S rRNA gene sequencing, followed by deep metagenomic and metatranscriptomic sequencing on a subset of samples chosen to be maximally biologically informative. In combination with downstream statistical biomarker discovery, this will allow the determination of microbial clades, genes, pathways, or transcripts associated with early life chemical exposure and subsequent adult glucose tolerance.