Early environments, epigenetics, and inflammation during pregnancy

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Environments early in life, during critical periods of development, have lasting effects on human biology. It is well established that nutritional and microbial environments in infancy shape the development and function of the human immune system, but the long term effects of early environments on the regulation of inflammation are not known. Inflammation is important because acute inflammatory responses provide protection against infection, but chronic or dysregulated inflammatory responses contribute to diseases that represent major public health burdens in the US, including cardiovascular disease, diabetes, and adverse pregnancy outcomes like low birth weight and preterm delivery. Scientists also have discovered that epigenetic processes - chemical modifications to genes that have enduring effects on their activity - are important biological mechanisms through which adults 'remember' the environments they experienced early in life. By taking advantage of a unique longitudinal birth cohort study in the Philippines, with more than 30 years of prospective data, this project will contribute to scientific understandings of how environments in infancy can influence the regulation of inflammation in adulthood.The project focuses on pregnant women, since inflammation is activated as part of normal pregnancy, but dysregulated inflammation contributes to preterm labor and delivery and fetal growth restriction. The research tests the hypothesis that undernutrition in infancy (prenatally and postnatally), and low levels of exposure to common microbes (e.g., bacteria in soil, untreated water), contribute to elevated levels of inflammation during pregnancy. It also tests the hypothesis that elevated inflammation during pregnancy leads to adverse birth outcomes (preterm delivery, lower birth weight). Lastly, the project investigates methylation of inflammatory genes - an epigenetic process that modifies gene expression - as a biological mechanism linking early environments, inflammation, and birth outcomes. Data and samples come from an ongoing birth cohort study in the Philippines that has followed the same individuals since their mothers were pregnant with them in 1983-84. The dataset is unique in having the time depth, range of measures, and environmental variation necessary to test the project's hypotheses. Results will shed new light on the developmental processes that contribute to chronic inflammation, with potential implications for well-being of the next generation. In addition, the focus on epigenetics in relation to the social and physical contexts of development will encourage a reconceptualization of the human genome as a dynamic substrate that incorporates information from the environment to alter its structure and function.