Early-Life Air Pollution Exposure Is Associated with the Infant Gut Microbiome and Fecal Metabolome in the First Two Years of Life.

INTRODUCTION: Obesity is a major public health concern because it increases the risk of numerous diseases, including cardiovascular disease and type 2 diabetes. Ambient and near-roadway air pollution has been associated with childhood obesity risk, independent of diet and physical activity. However, the biological mechanisms underlying these relationships remain unclear. Based on our previous work and existing literature, we hypothesized that exposure to air pollutants alters the developing infant gut microbiome and fecal metabolome, with implications for childhood obesity risk. In this study, we aimed to determine whether prenatal or early-life exposure to ambient air pollution and near-roadway air pollution is associated with the gut microbiome and fecal metabolome during the first 2 years of life.

METHODS: Our analysis had two components, both of which examined participants from the Southern California Mother's Milk Study, a Latino cohort in which we collected detailed information regarding maternal and child health during the first 24 months of life. Residential-based estimates of exposure to ambient particulate matter (particulate matter ≤2.5 µm and ≤10 µm in aerodynamic diameter: PM2.5 and PM10, respectively), nitrogen dioxide (NO2), and ozone (O3), as well as near-roadway air pollution (NOx), were modeled using residential address histories. High-throughput metagenomics and metabolomics were performed on stool samples collected at 1, 6, 12, 18, and 24 months of age. Overall, our sample included 207 unique individuals with gut microbiome data and 127 unique individuals with fecal metabolomics data. In the first analysis component, we examined the cross-sectional associations of pre- and postnatal exposure to ambient and near-roadway pollutants with the infant gut microbiome and fecal metabolome at 1, 6, 12, 18, and 24 months of age. In the second analysis component, we examined the longitudinal associations of pre- and postnatal exposure to air pollutants with the trajectory of the developing infant gut microbiome and fecal metabolome.

RESULTS: Our findings indicate that exposure to air pollutants during prenatal and postnatal periods is associated with significant changes in the developing gut microbiome and its metabolic output, as evidenced by perturbations in the fecal metabolome. These molecular alterations were evident in both cross-sectional and longitudinal analyses. The results suggest that early-life exposure to air pollution can disrupt the developmental trajectory of the gut microbiome, potentially leading to changes with substantial health implications. These findings underscore the importance of mitigating air pollution exposure during critical developmental periods to protect and promote gut health and overall well-being in infants.

CONCLUSIONS: We identified gut microbes and fecal metabolites associated with early-life exposure to air pollution. Many of these markers of gut bacterial composition and function have been linked to childhood obesity. These findings contribute to our understanding of mechanisms underlying the obesogenic effects of air pollutants in early life. Future work in this cohort will include integrated mixture and multi-omics analyses to explore the joint impact of air pollution exposure on the gut microbiome and fecal metabolome.