Household Triclosan and Triclocarban Use and the Developing Infant Microbiome

描述（由申请人提供）：婴儿微生物群在生命早期进化，第一年尤为重要。越来越多的研究人员推测，微生物获得的顺序和微生物组的多样性影响免疫、内分泌和代谢发育。因此，任何改变微生物组的东西都可能改变婴儿的生长，甚至是长期的健康和福祉。在过去的50年里，商业家用清洁和个人护理产品中的杀微生物剂在美国已经变得无处不在。最常见的是三氯生和三氯卡班（TCs），它们渗透在各种各样的商业产品中。由于它们的广泛使用，50%的地表水和75%的人类尿液样本中都含有三氯生。TCs具有广泛的活性，可杀死革兰氏阳性和革兰氏阴性细菌以及真菌。这些杀菌剂对人类微生物群的影响——更具体地说，对婴儿微生物群的影响——仍然未知。该小组目前正在进行一项纵向队列研究（STORK），以评估产时和儿童传染病对婴儿生长的影响。在STORK队列中，家庭被随机分配到含tc和不含tc的商业产品中，以确定这些化学物质是否会影响感染的发生率。在目前的建议中，这项工作将扩大到了解这些杀微生物剂对发育中的婴儿微生物组的影响。据推测，家庭使用TC会改变婴儿微生物群的进化，减少它们的多样性并改变它们的群落结构，可能导致

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.