Air Pollutants and the Gut Microbiota and Metabolome During Early Life: Implications for Childhood Obesity
Tanya L Alderete1, Elham Kazemian1, Farnaz Fouladi2, William Patterson1, Jeremy Sarnat3, Donghai Liang3, Howard Chang3, Kenneth Wright1, Michael Goran4, Fredrick Lurmann5
1University of Colorado Boulder, CO, USA; 2University of North Carolina Charlotte, NC, USA; 3Emory University, Atlanta, GA, USA; 4Children’s Hospital of Los Angeles, CA, USA; 5Sonoma Technologies Inc., Petaluma, CA, USA
Background: An improved understanding of the factors that trigger the development and progression of early life obesity is urgently needed. Beyond poor diet and low physical activity, studies suggest that early life exposures to ambient and near-roadway air pollution (NRAP) independently contribute to childhood obesity. Additionally, prenatal ambient and NRAP exposures have been associated with low birth weight, leading to increased infant weight gain and risk for childhood obesity. In previous work among adolescents, we found that increased NRAP exposure was correlated with the relative abundance of gut bacteria that have been associated with obesity and altered metabolism. Our overarching hypothesis is that increased exposure to air pollutants during pregnancy and early life will result in altered gut microbial profiles and fecal metabolites in infants, which will contribute to childhood obesity risk through changes in infant growth trajectories.
Methods: We will examine participants from the ongoing Mother’s Milk Study, which is examining the gut microbiota in 240 Hispanic mother-infant pairs at 1, 6, 12, 18, and 24-months postpartum. We will leverage and extend existing data to include: 1) ambient (PM2.5, NO2, O3) and NRAP exposures during critical developmental windows and 2) fecal metabolites from 5 a priori-selected metabolic pathways (short-chain fatty acid, lipid, amino acid, bile acid, and tryptophan metabolism) using repeated measures of fecal metabolomics in a subset of 120 infants.
Results: Our specific aims are to determine the extent to which prenatal and/or early life exposure to ambient and/or NRAP is: 1) cross-sectionally associated with the infant gut microbiota and fecal metabolites from 5 a priori-selected metabolic pathways at 1, 6, 12, 18, and 24-months of age, 2) longitudinally associated with alterations to the infant gut microbiota and the same suite of a-priori selected pathways, and 3) to determine whether infant gut bacteria and/or fecal metabolic pathways associated with increased ambient (PM2.5, NO2, O3) and/or NRAP exposures are also associated with infant growth trajectories under a mediation framework.
Conclusions: The proposed research will be the first human study to examine the effects of air pollutants on obesity and the potential mechanisms underlying these associations by assessing gut microbial composition and function in early life.