Environmental Chemicals, the Microbiome, and the Developing Brain

Abstract

While the link between in utero exposure to environmental chemicals and neurodevelopment has long been of interest to environmental epidemiologists, significant gaps remain in the literature, namely: 1) thousands of chemicals are produced and consumed in the United States every year, only some of which have been examined for neurodevelopmental effects, 2) chemicals are often examined in isolation even though the fetus is exposed to many chemicals at once, leaving the potential for synergistic effects, and 3) the mechanisms by which chemicals affect the brain are not fully elucidated. This dissertation aims to narrow each of these gaps. The first study addresses the first gap by examining the potential adverse neurocognitive effects of acetaminophen, a chemical that has only recently been explored for its neurodevelopmental effects. While previous studies using maternal report of exposure found a negative association with behavioral outcomes, this study, which uses a quantitative biomarker of acetaminophen exposure, finds no association. The second study addresses the second gap by investigating the combined effects of heavy metals and essential micronutrients on cognition and motor ability. It finds a nonlinear association between manganese and motor ability, and several sex-specific associations and interactions. Finally, studies three and four address the third gap by exploring the microbiome as a target of environmental exposures and a potential mediator of the association between chemicals and neurodevelopment. Study three finds that prenatal exposure to polybrominated diphenyl ethers and polychlorinated biphenyls is associated with changes to certain bacterial taxa in mid childhood, indicating the potential for long-term effects on the gut microbiome. The fourth study finds an association between prenatal caffeine exposure and beta diversity as well as specific taxa. Further, adjusting for the relative abundance of these taxa weakens the negative association between caffeine exposure and neurodevelopment measures. This dissertation addresses each of three significant gaps in the environmental epidemiology neurodevelopment literature. It demonstrates the importance of considering multiple exposures concurrently, particularly those that may act through similar mechanisms. Notably, this dissertation proposes the gut microbiome as a novel mechanism by which environmental exposures affect neurodevelopment. This paradigm should inform future environmental epidemiological research.