This project will test the innovative hypothesis that developmental exposure to environmental toxicants can alter gut microbiome assembly and succession to consequently result in impaired behavior and cognition. The alarming rise in behavioral and cognitive disorders is linked to early life exposure to environmental chemicals, such as benzo[a]pyrene (BAP), the globally ubiquitous pollutant on which this project focuses. While the mechanisms underlying these impairments remain poorly defined, prior work implicates a dysbiotic gut microbiome. This project will define how early life exposure to BAP alters the development of gut microbiome structure and function and how these alterations relate to behavior. It will also couple high-throughput culturing with a scalable, germ-free animal model (zebrafish) to comprehensively measure the behavioral impacts of BAP-sensitive gut microbes and their metabolites. This project also quantifies how developmental BAP exposure alters the microbiome-behavior axis in subsequent generations. Consequently, the proposed research holds great potential to transform our understanding of the causes of behavior impairment and reveal new candidates, in the forms of gut microbes and metabolites, for normalizing behavior development.
Developmental benzo[a]pyrene exposure impairs behavior throughout lifespan and across generations through unknown mechanisms. This project will discover gut microbes and their metabolites that are both sensitive to developmental BAP exposure and critical to normal behavior development. The long-term goals of this project are to determine if disruption of the assembly and development of the gut microbiome underlies the intergenerational rise in behavioral and cognitive disorders and resolve preventative and therapeutic strategies for normalizing behavior development.
