Early life metal exposure, the gut microbiome, and neurodevelopment in childhood

PROJECT SUMMARY I am an environmental epidemiologist and microbiome researcher with a primary research interest in the role of the human microbiome between environmental exposures and human health, including neurological outcomes. The goal of this proposal is to obtain training and acquire the skills needed to continue to build my academic research career by linking early life metal exposure, the gut microbiome and metabolome in childhood, and neurodevelopmental measures of attention. For this proposal, I plan to train with an expert team of mentors, collaborators, and advisors with transdisciplinary expertise in exposomics, exposure biology, neurodevelopment, biostatistics, metabolomics, epidemiology, and microbiome research. The proposed training plan includes clinical and laboratory rotations, coursework, seminars and meetings, conferences, and 1-on-1 tutorials with mentors and advisors, covering research and career development topics. This training will provide skills and knowledge in the areas of neurodevelopment, and exposomics, including exposure biology and multi-omics analysis. Upon completion of this training plan, I will be able to achieve my long-term career goal of becoming an independent researcher focused on the inter-relationships among environmental exposures, the microbiome, and neurodevelopment. To that end, I propose leveraging the use of the established Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) birth cohort, based in Mexico City, and adding microbiome analysis. Specifically, I will: 1) train with Dr. Arora in exposure biology and analysis of baby teeth as a biomarker of early life metal exposure; 2) train with Dr. Wright, in collaboration with Dr. Shamesh, in neurodevelopmental assessment, principals of neurotoxicology, and their use in epidemiologic studies; 3) train with Dr. Faith in metagenomic analysis, 4) integrate biostatistical assessment of mixtures and high dimensional data, guided by Dr. Gennings; 4) learn about stool metabolomic analysis methodology with Dr. Walker; 5) work with Dr. Tellez-Rojo to facilitate stool sample collection and data analysis in PROGRESS. I will use these training and research activities to integrate the microbiome into an exposomic analysis of neurodevelopment. I will use the research and career development training I receive to establish myself as an independent investigator with a tenure track faculty position, able to secure R01 funding. This research proposal combines innovative measures of exposure, novel data analysis approaches, and high resolution omics analysis to address gaps in the understanding of timing and potential mechanisms by which metal exposures, and the gut microbiome and metabolome, are associated with neurodevelopmental measures of attention. The proposed research and training plan builds the foundation for an independent research career that aims to clarify the links between environmental exposures and neurodevelopment, via the human microbiome.