Household Triclosan and Triclocarban Use and the Developing Infant Microbiome

描述(由申请人提供)：婴儿的微生物组在早期生命中进化，第一年特别重要。越来越多的研究人员推测，微生物获取的顺序和微生物组的多样性影响着免疫学、内分泌学和新陈代谢的发展。因此，任何改变微生物组的东西都可能改变婴儿的成长，甚至改变婴儿的长期健康和福祉。在过去的50年里，商业家居清洁和个人护理产品中的杀菌剂在美国变得无处不在。最常见的杀菌剂--三氯生和三氯卡班(TCS)--渗透到各种商业产品中。由于三氯生的广泛使用，50%的地表水和75%的人类尿样中发现了三氯生。TCS具有广泛的活性，可以杀死革兰氏阳性和革兰氏阴性细菌以及真菌。这些杀生剂对人类微生物群的影响--更具体地说对婴儿微生物区系的影响--仍不清楚。该团队目前正在进行一项纵向队列研究(STOK)，以评估产中和儿童传染病对婴儿生长的影响。在斯托克队列中，家庭被随机分配到有和没有TCS的商业产品中，以确定这些化学物质是否影响感染的发生率。在目前的提案中，这项工作将扩大到了解这些杀菌剂对发育中的婴儿微生物组的影响。据推测，家庭使用TC将改变婴儿微生物区系的进化，减少它们的多样性，改变它们的群落结构，可能导致 生长、新陈代谢和免疫功能的差异。因此，具体目标是确定婴儿微生物区系的成员和结构是否与家庭TC使用相关。为了评估这一特定目标，将对从母亲及其新生儿采集的粪便、唾液和皮肤拭子样本进行深度16S rDNA测序。每四个月收集一次样本，直到孩子们三岁。将对尿液进行三氯生暴露检测，并每周获取有关儿童生长发育、传染病症状和抗生素使用的信息。所有这些工作都将在之前收集的样本上进行，不需要额外的人类受试者接触。分析将包括：基于杀菌剂随机化的儿童微生物区系的意向治疗比较；基于尿三氯生水平高低的儿童微生物区系暴露比较；以及按杀菌剂ARM分层的母亲及其子女微生物区系的比较。不断扩大的研究表明，发育早期的环境暴露会在以后的生活中形成疾病的易感性。环境暴露和宿主结果之间的关系在多大程度上实际上是由微生物区系调节的，这是一个巨大的未知数。这项研究将为探索这一新的研究前沿奠定基础。

DESCRIPTION (provided by applicant): The infant microbiome evolves over early life, with the first year being of particular importance. Increasingly, investigators speculate that the sequence of microbial acquisition and the diversity of the microbiome influence immunologic, endocrinologic and metabolic development. Thus, anything that modifies the microbiome may alter infant growth and even long-term health and well-being. Over the last 50 years, microbicides in commercial household cleaning and personal care products have become ubiquitous in the U.S. The most common--triclosan and triclocarban (TCs)-permeate a vast assortment of commercial products. Due to their widespread use, triclosan is found in 50% of surface water and 75% of human urine samples. TCs have a broad spectrum of activity, killing Gram-positive and Gram-negative bacteria as well as fungi. The effects of these biocides on the human microbiome--and more specifically on the microbiota of infants--remain unknown. This team is currently conducting a longitudinal cohort study (STORK) to assess the consequences of intrapartum and childhood infectious diseases on infant growth. Within the STORK cohort, households were randomized to commercial products with and without TCs to determine whether these chemicals affect the incidence of infection. In the current proposal, this work will be expanded to understand the effects of these microbicides on the developing infant microbiome. It is hypothesized that household TC use will modify the evolution of infant microbiota, reducing their diversity and altering their community structure, potentially leading to differences in growth, metabolism and immune function. The specific aim, then, is to determine whether membership and structure of infant microbiota correlate with household TC use. To assess this specific aim, deep 16S rDNA sequencing will be conducted on collected stool, saliva, and skin swab samples from mothers and their newborns. Samples will be collected every four months until the children reach the age of three years. Urine will be tested for triclosan exposure and information on child growth, infectious diseases symptoms, and antibiotic use will be accessed weekly. All this work will be done on previously collected samples with no additional human subjects contact. Analyses will include: intention-to- treat comparisons of the children's microbiota based on microbicide randomization; exposure comparisons of the children's microbiota based on high and low urinary levels of triclosan; and a comparison of mothers' and their children's microbiota stratified by microbicide arm. An enlarging body of work indicates that environmental exposures early in development shape susceptibility to disease later in life. How much of the relationship between environmental exposure and host outcome is actually mediated by microbiota is a great unknown. This study will lay groundwork for exploring this new frontier of research.