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