Pre- and Postnatal Exposure to Air Pollutants and the Gut Microbiome: Implications for Brain Development in Early and Mid-Childhood

ABSTRACT Early life exposure to air pollution (AP), which disproportionately affects underserved communities, is thought to disrupt cognitive, emotional, and behavioral development. Human studies show that exposure during the prenatal and early postnatal periods are associated with developmental delays, autism, more severe attention- deficit hyperactivity disorder, depression, and anxiety. Increasing evidence also suggests that exposure to AP is associated with variation in the human gut microbiome, which other evidence suggests can alter brain physiology and cognitive development. Despite these prior findings, no studies have considered the role of the gut microbiome as a potential mediator of the effects of AP exposure on brain development and neurodevelopment outcomes in early life. Further, human studies have focused on the associations of AP exposure with cognitive outcomes at a single timepoint, and very few have examined AP-induced changes in brain structure and function. Our overarching hypothesis is that AP exposure adversely impacts brain and neurodevelopmental outcomes, and that these effects are partially explained by alterations in the gut microbiome. Our preliminary data show that AP exposure is associated with a) poorer Bayley’s motor scores at 24-months, b) adverse gut bacterial and fecal metabolic profiles at 6-months, and c) brain tissue microstructure and blood flow; and d) the newborn gut microbiome is associated with brain measures. Our multidisciplinary team of investigators proposes to test our hypothesis in a cohort of 200 Latino mother-infant pairs, with detailed assessments of maternal health and nutrition, infant growth, and early feeding practices at 1, 6, 12, 18, and 24-months of age. Child cognitive, language, and motor capacities were previously assessed using Bayley Scales at 24 months. With separate NIH funding, we are currently collecting follow-up measures at 6yr, including anthropometric measures, nutritional information, and current and cumulative environmental exposures to ambient and near-roadway AP. We will use archived (1, 6, 12, 18, 24-months) and newly collected stool samples (6yr) to examine gut bacterial species and fecal metabolic pathways (SCFA, lipid, amino acid, bile acid) that can alter brain development. Our specific aims are to determine the extent to which early life exposure to AP is associated with neurodevelopmental outcomes and brain measures (Aim 1), and with the gut microbiome and fecal metabolome (Aim 2) in early- and mid-childhood. We further aim to determine whether air pollution-associated gut microbial profiles and fecal metabolic pathways mediate the associations of AP exposure with neurodevelopmental outcomes and brain measures (Aim 3). This study offers a unique opportunity to advance our understanding of the harmful effects of early life exposure to AP. Results may also suggest interventions that could prevent or attenuate neurodevelopmental disorders, such as limiting prenatal and early life AP exposure or other novel interventions to promote or quell growth of specific gut bacteria.