Impact of Urbanicity on Infant Brain Structure and Function via the Gut-Brain Axis

About This Grant

Over 55% of the world’s population resides in urban areas, a figure projected to rise to 68% by 2050. Urban living is linked to an elevated risk of mental illness in adults, likely due to the combined effects of physical and social stressors. Exposure to urban environments during infancy and early childhood, a critical period of brain development, is associated with higher risks of schizophrenia, autism, substance dependence, and mood and anxiety disorders. These vulnerabilities likely originate early in life when the brain is rapidly developing and highly sensitive to environmental influences. However, the mechanisms by which urbanicity affects early brain development remain poorly understood. Our primary objective is to address this critical gap by identifying the neural correlates of urbanicity in infants and investigating the gut microbiome as a potentially modifiable mechanism in this relationship. The gut microbiome, a diverse community of microorganisms in the digestive tract, plays an important role in regulating stress responses. Our central hypothesis is that urban environments alter infants’ gut microbiome composition and function. Gut microbiome changes, in turn, disrupt neurodevelopmental processes occurring during the first year of life, altering brain structure and connectivity, and increasing the risk of mental health challenges. To test this hypothesis, we will use data from the NIH-funded Organization for Imaging Genomics in Infancy (ORIGINs) consortium, which includes over 4,000 infants and young children from six countries with high-resolution structural MRI, diffusion tensor imaging, and resting-state fMRI scans. Urban environment variables will be assessed using geocoded residential addresses and will encompass both physical and social features, including air quality, green spaces, blue spaces (water bodies), street connectivity, and access to specific facilities, infrastructures, and destinations such as health care, supermarkets, and convenience stores. We will test whether urbanicity is associated with brain structure and function in systems related to stress, reward, and emotional processing. Gut microbiome data, already extracted and sequenced from a subset of ORIGINs cohorts, will be analyzed to generate diversity metrics and assess their associations with urban exposure, as well as their potential mediating role in the relationship between urban exposure and neuroimaging phenotypes. This research is significant because it will provide critical insights into biological pathways linking urbanicity to early brain and gut development, guiding strategies to create healthier urban environments that reduce psychiatric risks and promote mental health.