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.

Public Health Relevance

Triclosan and triclocarban are broad spectrum microbicides found in a vast array of common household and personal cleaning products such as soap and toothpaste. Present in the urine of 75% of the U.S. population, this chemical may well influence the diversity of the human microbiome both on the skin and in the gut, potentially affecting not only a baby's developing immune system but her or his future health profile. We will evaluate the effects of triclosan and triclocarban exposure on the establishment of the developing infant microbiome over the first three years of life, taking into consideration the maternal microbiome, that of the household environment and the confounding effects of important life events.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21ES023371-02
Application #
8791686
Study Section
Special Emphasis Panel (ZES1-JAB-J (MB))
Program Officer
Chadwick, Lisa
Project Start
2014-01-14
Project End
2016-12-31
Budget Start
2015-01-01
Budget End
2015-12-31
Support Year
2
Fiscal Year
2015
Total Cost
$287,578
Indirect Cost
$94,367
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Ribado, Jessica V; Ley, Catherine; Haggerty, Thomas D et al. (2017) Household triclosan and triclocarban effects on the infant and maternal microbiome. EMBO Mol Med 9:1732-1741
Ley, Catherine; Pischel, Lauren; Parsonnet, Julie (2017) Triclosan and triclocarban exposure and thyroid function during pregnancy-A randomized intervention. Reprod Toxicol 74:143-149
Poole, Angela C; Pischel, Lauren; Ley, Catherine et al. (2016) Crossover Control Study of the Effect of Personal Care Products Containing Triclosan on the Microbiome. mSphere 1: