ABSTRACT
Childhood obesity is a high priority public health issue as it increases the risk of co-morbid diseases, including
cardiovascular disease, fatty liver disease, and type 2 diabetes. An improved understanding of the factors that
trigger the development of early life obesity is urgently needed. This is especially important among Hispanics, a
minority group with high rates of obesity in early life. Beyond poor diet and a lack of physical activity, early life
exposure to environmental chemicals, which are higher in underserved communities, independently contribute
to childhood obesity. Human studies show that even at low levels of exposure during pregnancy, poly- and
perfluoroalkyl substances (PFAS) are associated with rapid infant weight gain and greater risk for childhood
obesity. Postnatally, breastfeeding is a primary source of inadvertent PFAS transmission to infants, potentially
offsetting some benefits of extended breastfeeding. Recent findings suggest that the developing gut microbiome
is exposed to breast milk PFAS, which may alter gut bacteria and fecal metabolites that contribute to obesity.
Despite this, human studies have largely focused on prenatal PFAS exposure, and no prior studies have
examined the effects of breast milk PFAS on rapid infant growth and the gut microbiome during infancy, a critical
period in which interventions have the potential to prevent the development of childhood obesity. Our overarching
hypothesis is that higher concentrations of breast milk PFAS contribute to more rapid infant growth and childhood
obesity risk, and that these effects are explained by alterations in the composition and function of the infant gut
microbiome. This hypothesis is based on results from our preliminary data, which demonstrate that infant gut
bacteria are associated with infant weight and breast milk PFAS at 6-months of age. Our multidisciplinary team
of investigators propose to test this hypothesis in a cohort of 208 Hispanic mother-child pairs with assessments
of child growth at 1, 6, 12, 18, 24, and 36-months as well as at 6yr of age. This study will measure breast milk
PFAS concentrations and characterize the infant gut microbiome and fecal metabolome using archived breast
milk and stool samples at 1- and 6-months to advance our mechanistic understanding of the obesogenic effects
of PFAS exposure while accounting for prenatal PFAS exposure using newborn dried blood spots. Our aims are
to determine the extent to which early life exposure to breast milk PFAS are associated with: 1) child weight from
1-month to 6 years (Aim 1A) and the risk of rapid growth and childhood obesity (Aim 1B) as well as 2) changes
in gut microbial profiles and fecal metabolites (Aim 2). Our ultimate goal (Aim 3) is to integrate breast milk PFAS
exposure, gut microbiome, and fecal metabolomics profiles to identify subgroups of children that are at increased
risk for rapid growth and obesity. This study offers a unique opportunity to advance our understanding of breast
milk PFAS and may identify preventive measures that could be used to offset obesity-risk, including screening
for breast milk PFAS and the use of probiotics to promote growth of beneficial gut bacteria in early life.
