Project Summary/Abstract American Indian (AI) children have high rates of chronic disease development including asthma, obesity and type 2 diabetes. The intestinal microbiome is a potential common contributor to all of these, yet no research currently exists examining the intestinal microbiome in AI children as a possible link to chronic disease development. This proposal includes several analyses to assess the contribution of race as well as prenatal exposures and early childhood environment to the colonization of the intestinal microbiome as well as possible links to chronic disease risk factors. The microbiome will be assessed both shortly after birth using stored meconium samples and again at three years of age. Longitudinal samples will help to delineate long term effects of prenatal exposures from effects of the early life environment and racial background. In addition to its relationship to exposures, this proposal will also explore links between the intestinal microbiome and risk factors for chronic disease, providing information about possible intervention strategies in at-risk populations. This is especially important for AI children as the risk for development of chronic disease is elevated and current prevention efforts have not achieved a reduction in risk. Thus, there is an urgent need to develop models to better understand how exposures relate to biological markers that can be used for disease prediction and intervention development.