Abstracts

Angelico Mendy, Ph.D., University of Cincinnati

Title: Early Life Exposure to Replacement Flame Retardants and Child Respiratory Outcomes (2MB)

Abstract: Due to environmental and health concerns, polybrominated diphenyl ethers (PBDEs) previously used as flame retardants were phased out in the U.S. starting in 2004 and substituted with organophosphate (OPFRs) and replacement brominated flame retardants (RBFRs). Inhalation of contaminated house dust and vapor as a route of exposure to these chemicals has raised concerns for respiratory health due to their ability to cause irritation, oxidative stress, bronchoconstriction, endocrine disruption, and epigenetic changes. Yet, the association of these exposures with respiratory outcomes is unknown, especially in children who may be at higher risk due to higher exposure to the chemicals. The goal of this project is to test the hypothesis that childhood and in utero exposure to OPFRs and RBFRs is associated with respiratory symptoms and impaired lung function in the Health Outcomes and Measures of the Environment (HOME) Study, a multiethnic pregnancy and birth cohort from the Greater Cincinnati, Ohio, with environmental exposures similar to U.S. national averages.

EHS Core Center Affiliation: University of Cincinnati, CEG

Shelly Buffington Ph.D., The University of Texas Medical Branch

Title: Host-microbe Interactions Regulating the Multigenerational Impact of Maternal High-fat Diet on Descendant Social Behavior (3MB)

Abstract: Neurodevelopmental disorders, including autism spectrum disorder (ASD), are highly heritable; however, consensus is growing behind a two-hit hypothesis in which environmental factors serve as a tipping point in disease manifestation in genetically predisposed individuals. Among environmental exposures, those that impact the maternal gut microbiome–another source of heritable genetic variability–during pregnancy are emerging as key modulators of neurodevelopment and behavioral outcomes in offspring. Diet is the primary driver of microbiome composition. Previously, Buffington and fellow researchers reported that maternal high-fat diet resulted in dysbiosis of the gut microbiome, social dysfunction, and underlying synaptic plasticity deficits in male offspring. In recent work, they sought to determine whether high-fat diet-induced dysbiosis of the maternal gut microbiome during pregnancy could be causal in offspring social dysfunction and whether its effects could be observed in generations beyond F1. Building on their previous findings, Buffington and fellow researchers reasoned that maternal high-fat diet would likewise induce long-term dysbiosis of the female offspring (F1) gut microbiome, thereby recapitulating critical aspects of the adverse in utero environment experienced by the F1 males. If this adverse in utero environment engendered by diet-induced dysbiosis of the maternal gut microbiome was causal in the neurodevelopmental deficits in the F1 males, then inherited dysbiosis in the F1 females could result in social dysfunction in the F2 generation, in the absence of any dietary challenge. Here, Buffington will discuss the results of this study which identify a critical link between grandmaternal high-fat diet, specific microbially-derived metabolites, stability of descendant microbial communities in response to environmental pressures, and maladaptive behaviors, with implications for both host disease susceptibility and therapeutic targeting of the gut microbiome.

EHS Core Center Affiliation: Baylor College of Medicine, GC-CPEH