Gut Microbiome in Adults with Early Life Exposures to Environmental Chemicals

描述（申请人提供）：将在超过500名年轻成年人中检查微生物组在发育和出生后暴露于环境化学品方面的特征以及与葡萄糖代谢异常标志物的可能关联，这些年轻成年人是1986-1987年在法罗群岛建立的独特出生队列的成员，一个接触环境化学品的范围异常广泛的社区。将邀请28岁的队列成员进行临床检查，并采集粪便样本。在出生时和7岁、14岁和22岁时的既往临床检查中获得了关于既往化学品暴露、饮食、病史和其他协变量的数据，其中84%-90%的队列（N = 1，000）参与了该研究。这些数据包括甲基汞、多氯联苯、DDE和全氟化合物的暴露情况。临床检查将包括葡萄糖耐量试验。这些受试者的肠道微生物组的结构和功能将在两个阶段的过程中进行评估。每个样本中存在的微生物将通过16 S rRNA基因测序确定，然后对选择的样本子集进行深度宏基因组和元转录组测序，以获得最大的生物信息。结合下游统计生物标志物发现，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进化枝、基因、途径或转录物。

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.