Triclosan, pubertal hormones, and the gut microbiome: implications for neurobehavior

三氯生、青春期激素和肠道微生物组：对神经行为的影响

基本信息

批准号：
10590197
负责人：
Hannah Elizabeth Laue
金额：
$ 11.02万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10590197
关键词：
Academic achievement Address Adolescence Adolescent Adolescent Behavior Adult Affect Age Anxiety Attention Attention deficit hyperactivity disorder Award Behavior Behavior assessment Biological Birth Brain Chemical Exposure Child Childhood Complement DNA Data Data Collection Dehydroepiandrosterone Sulfate Development Disease Educational workshop Endocrine Disruptors Endocrinology Environment Environmental Epidemiology Environmental Impact Environmental Risk Factor Estradiol Etiology Exposure to Feces Female Follicle Stimulating Hormone Future Gonadal Steroid Hormones Growth Health Hormonal Hormonal Change Hormones Human Individual Infant Learning Link Literature Luteinizing Hormone Measurement Measures Mediating Mediation Mental Depression Mental Health Mentors Mentorship Metabolism Methods Microbe Modeling National Institute of Environmental Health Sciences Outcome Participant Perinatal Phase Play Predisposition Pregnancy Problem behavior Puberty Research Research Personnel Research Priority Risk Factors Role Sampling Serum Shapes Social Functioning Strategic Planning Structure Symptoms System Testing Testosterone Therapeutic Toxic Environmental Substances Toxic effect Training Triclosan Visit Work antimicrobial behavioral health behavioral outcome boys cohort consumer product dysbiosis environmental chemical fecal microbiome girls gut bacteria gut microbiome gut microbiota gut-brain axis informant interest metabolome metagenomic sequencing microbial community microbiome microbiome alteration microbiome analysis microbiome composition neurobehavior neurobehavioral novel prospective response sex skills urinary

项目摘要

PROJECT SUMMARY Despite potential lifelong consequences of gut microbiome dysbiosis, little is known about environmental factors that influence its diversity and composition, including windows of susceptibility to exposure. The gut microbiome performs essential functions for human health, and is related to neurobehavioral development via the gut-brain axis. While a few studies have examined the infant/adult microbiome in the context environmental epidemiology, the adolescent microbiome has not received attention, even though it occurs in a period of rapid development when the hormonal milieu is changing, and internalizing behaviors often emerge. The proposed project aims to address these gaps by examining the relations between exposure to triclosan—an antimicrobial and endocrine disrupting compound—pubertal hormones, the adolescent microbiome, and neurobehavior. This work will leverage the Health Outcomes and Measures of the Environment Study, a longitudinal birth cohort with rich data collection including quantification of urinary triclosan at 10 visits from early gestation through 12Y, pubertal hormones, the serum metabolome, and behavior. Crucial to this project, participants provided stools at 12Y. During the K99 phase, fecal DNA will be sequenced to profile microbial communities, which will be used to identify windows of susceptibility to triclosan (Aim 1). Dr. Laue will assess the role of hormones in shaping the microbiome, including whether they mediate or modify the triclosan-microbiome association (Aim 2), and examine the relationship between the adolescent microbiome and behavior (Aim 3a). During the R00 phase, microbiome and behavioral assessment at 18Y to inform our understanding of the longitudinal association between the microbiome and behavior (Aim 3b). Dr. Laue will characterize the role of the serum metabolome in the microbiome-behavior association (Aim 4) and will determine whether bacterial features mediate or modify the association between triclosan and adolescent behavior (Exploratory Aim 5). To complete this research, Dr. Laue will complement her expertise in environmental epidemiology and the infant microbiome with extensive training under the guidance of her mentorship team (Dr. Margaret Karagas— primary mentor, Dr. Joseph Braun—co-mentor, Dr. Juliette Madan—advisor, Dr. Abby Fleisch—advisor, Dr. Amy Willis—advisor). Dr. Laue will learn from coursework, workshops, and individualized trainings in 1) processing microbiome data and microbiome measurement error, 2) multiple informant modeling and other methods for identifying windows of susceptibility, 3) causal mediation, 4) pediatric endocrinology, and 5) neurobehavior. This award will prepare Dr. Laue to be an independent researcher specializing in environmental epidemiology and the adolescent microbiome. Dr. Laue’s research will fill a critical gap in the environmental epidemiological literature, namely what role the adolescent microbiome and metabolome play in the relationship between a ubiquitous environmental toxicant (triclosan) and neurobehavior.

项目概要尽管肠道微生物群失调可能造成终生后果，但人们对环境问题知之甚少。影响其多样性和组成的因素，包括暴露的易感性窗口。微生物组对人类健康发挥重要作用，并通过以下方式与神经行为发育相关虽然一些研究已经在环境背景下检查了婴儿/成人微生物组。流行病学方面，青少年微生物组尚未受到关注，尽管它发生在快速增长的时期当荷尔蒙环境发生变化时，就会出现内化行为。该项目旨在通过检查接触三氯生（一种抗菌药物）之间的关系来解决这些差距以及内分泌干扰物——青春期激素、青少年微生物组和神经行为。这项工作将利用健康结果和环境措施研究，这是一项纵向诞生的研究具有丰富数据收集的队列，包括从妊娠早期起 10 次就诊时尿液三氯生的定量通过 12Y、青春期激素、血清代谢组和行为对于该项目至关重要，参与者。提供 12 岁的粪便在 K99 阶段，将对粪便 DNA 进行测序以分析微生物群落，将用于确定对三氯生的敏感性窗口（目标 1）。 Laue 博士将评估其作用。塑造微生物组的激素，包括它们是否介导或改变三氯生微生物组关联（目标 2），并检查青少年微生物组与行为之间的关系（目标 3a）。在 R00 阶段，在 18 岁时进行微生物组和行为评估，以帮助我们了解微生物组与行为之间的纵向关联（目标 3b）将描述微生物组的作用。微生物组-行为关联中的血清代谢组（目标 4），并将确定细菌是否特征介导或改变三氯生与青少年行为之间的关联（探索性目标 5）。为了完成这项研究，劳厄博士将补充她在环境流行病学和在她的导师团队（玛格丽特·卡拉加斯博士）的指导下，婴儿微生物组接受了广泛的培训—— 首席导师 Joseph Braun 博士——共同导师，Juliette Madan 博士——顾问，Abby Fleisch 博士——顾问，Dr. 艾米·威利斯 (Amy Willis) — 顾问）劳厄博士将通过以下方面的课程、研讨会和个性化培训进行学习：处理微生物组数据和微生物组测量误差，2）多线人建模等识别易感性窗口的方法，3) 因果调节，4) 儿科内分泌学，以及 5) 该奖项将使劳博士成为一名专门研究神经行为的独立研究员。环境流行病学和青少年微生物组的研究将填补这一领域的关键空白。环境流行病学文献，即青少年微生物组和代谢组在其中发挥什么作用普遍存在的环境毒物（三氯生）与神经行为之间的关系。