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

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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.