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Air pollutants and the gut microbiota and metabolome during early life: Implications for childhood obesity

Principal Investigator: 

University of Colorado, Boulder

This New Investigator Award study will investigate whether prenatal and/or early-life exposure to air pollutants affects the infant gut microbiota and fecal metabolome, thereby altering infant growth trajectories in the first two years of life. Dr. Alderete plans to study this in an ongoing longitudinal cohort of Hispanic mother-infant pairs in California with existing validated clinical assessments of infant growth trajectories. She will also use gut microbial profiling and high-resolution fecal metabolomics profiles to understand the mechanisms underlying the obesogenic effects of air pollutants in early life.

Funded under

Poster abstract for HEI Annual Conference 2023

The Infant Fecal Metabolome: Proposing a Mechanistic Link Between Prenatal Air Pollution Exposure and Childhood Obesity Risk

Elizabeth A. Holzhausen1, Bridget Chalifour1, Natalie Shen2, ViLinh Tran2, Zhenjiang Li2, Jeremy A. Sarnat2, Fredrick Lurmann3, Howard H. Chang2, Dean P. Jones2, Michael I. Goran4, Donghai Liang2, Tanya L. Alderete1

1University of Colorado Boulder, Boulder, CO, USA
2Emory University, Atlanta, Georgia, USA
3Sonoma Technology Inc., Petaluma, CA, USA
4Children’s Hospital Los Angeles, Los Angeles, CA, USA

Background. Exposure to ambient air pollution (AAP) has been shown to contribute to obesity, independent of poor diet and inactivity. Further, prenatal AAP is associated with negative infant outcomes including low birth weight, which can lead to rapid growth and increased risk of childhood obesity. Despite this, the biological mechanisms driving these relationships are not well understood. Pre- and post- natal AAP have been linked with infant gut microbiome composition. The fecal metabolome may represent a functional readout of gut bacteria, with potential systemic metabolic effects. Therefore, this study sought to assess whether prenatal AAP exposure was associated with infant fecal metabolites at 1-month of age.

Methods. Participants included 124 mother-infant dyads from the Southern California Mother’s Milk Study. Pregnancy AAP exposure (i.e., NO2, PM2.5, and PM10) was modeled using residential addresses; infant fecal metabolites were measured via untargeted liquid chromatography high-resolution mass spectrometry. Linear models were used to estimate the relationship between AAP and the logged intensity of fecal metabolites, adjusting for infant sex, socioeconomic status, season, and breastfeeding. The Benjamini-Hochberg procedure was used to adjust for multiple testing and results were considered statistically significant if PBH < 0.05 for metabolites with validated identification and PBH < 0.10 for all untargeted features. A pathway analysis of untargeted metabolites associated with AAP was conducted using Mummichog.

Results. Among validated metabolites, pregnancy NO2, PM2.5, and PM10 exposure was associated with 11, 5, and 7 fecal metabolites at 1-month of infant age, respectively (all PBH < 0.05). Overall, AAP was inversely associated with metabolites belonging to amino acid and fatty acid metabolism pathways, while metabolites belonging to the carbohydrate metabolism pathway were positively associated with AAP.  Among untargeted metabolic features, pregnancy exposure to NO2, PM2.5, and PM10 was associated with 49, 86, and 142 metabolic features, respectively (all PBH < 0.10). These metabolic features belonged to metabolic pathways including tryptophan and amino acid metabolism.

Conclusions. This study identified several metabolic pathways associated with prenatal air pollution exposure. For example, amino acid metabolism – a pathway involved in satiety, leptin, adiposity, and body weight – was inversely associated with PM10, PM2.5, and NO2 in both validated and untargeted analyses. In untargeted analyses, PM2.5 was associated with tryptophan metabolism, which has been liked with adipose tissue inflammation and satiety. These findings offer preliminary evidence that prenatal exposure to AAP may impact the infant fecal metabolome, which may contribute to some of the known associations between AAP and childhood obesity. Future work in this cohort will include longitudinal assessment of the fecal metabolome in the context of the developing gut microbiome.