Perfluoroalkyl Substances and the Gut Microbiome and Fecal Metabolome: Implications for Obesity Risk in Hispanic Children

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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.