Clearing the air on pollutant disruptions of the gut-brain axis: Developmental exposure to Benzo[a]pyrene disturbs zebrafish behavior and the gut microbiome in adults and subsequent generations
Developmental exposure to benzo[a]pyrene (BaP), a ubiquitous environmental pollutant, has been linked to various toxic effects, including neurodegenerative disorders and, most recently, multigenerational behavioral impairment. While the specific mechanisms driving BaP neurotoxicity are not fully understood, recent work highlights two important determinants of developmental BaP neurotoxicity: (1) the aryl hydrocarbon receptor (AHR), which is responsible for inducing host metabolism of BaP, and (2) the gut microbiome, which may interact with BaP to affect its metabolism, or be perturbed directly by BaP to yield disruptions to the gut-brain axis. To explore the role of AHR, the gut microbiome, and their interaction on BaP-induced neurotoxicity, we utilized the zebrafish model. We sought to determine (1) how exposure to BaP and developmental expression of AHR2, a key gene in the zebrafish AHR pathway, link to adult zebrafish behavior, (2) how these same variables associated with the structure and function of the adult zebrafish gut metagenome, and (3) whether these associations were multigenerational. This finding revealed a reticulated axis of association between BaP exposure, developmental AHR2 expression, the zebrafish gut metagenome, and behavior. Our results also indicate that AHR2 is a key mediator of how BaP elicits neurotoxicity and microbiome dysbiosis. Additionally, this axis of association manifests inter- and transgenerationally, suggesting that exposure to BaP may yield dysbiotic and neurodevelopmental impacts on subsequent generations. These findings demonstrate the power of utilizing the zebrafish model to study pollutant-metagenome interactions and elucidate the role of specific host genes in the neurotoxicity and dysbiosis.