. The Exposome and the Developmental Origins of Lifelong Health: Pre-, Peri- and Postnatal Microbiome Metabolome Development

摘要

The roles of human-associated microbial communities in health are appreciated, but we lack a mechanistic understanding of the differences between health promoting or dysbiotic/detrimental microbial communities and how the microbiome develops over time. Large scale epidemiological studies of environmental toxicants and their impact on human health benefit from thorough investigation of the bidirectional relationship between toxicants and the human microbiome/metabolome. Ultimately, the effects of microbial communities on health outcomes is particularly evident in the pre-, peri-/post and neonatal period during the critical window of microbial training of the developing immune system. Data generated by us and others indicate that microbial community development and metabolism can be influenced by coexisting microbes in often unexpected ways, and we hypothesize that these networks of microbial metabolic interactions drive community development and function. In our Children's Center at Dartmouth, we combine targeted microbial sequencing, metagenomics and metabolomics analyses, computational methods, and laboratory-based studies to identify microbial community structures over time, and microbe-produced metabolites that influence community development and stability. Our group investigates the relationships between exposures (e.g. environmental toxicants such as arsenic, dietary exposures, medications/antibiotics, delivery mode), the developing microbiome and metabolome in pregnancy, infancy and early childhood, and associations with health outcomes in a large molecular epidemiological study of 2,000 mother-infant dyads (4,000 subjects), the New Hampshire Birth Cohort Study. Our long-term goal is to rigorously test associations between microbiome development, community metabolism and host physiology, and to apply this knowledge to the discovery of strategies for health promotion.