PS 5-70 - Gut microbiome dynamics and functional traits in zebrafish perturbed by chemical toxicant (Benzo[a]pyrene) exposure in host gene-dependent manner over multiple generations

Abstract: Industrial modernization has led to increased exposure to the chemical toxicant Benzo[a]pyrene (BaP), which can be produced via coal burning and high-heat cooking. Past studies have demonstrated the effect of BaP exposure on human health and early development. Model organism studies have uncovered a link between early development exposure to BaP, gut microbiome dynamics, and host behavior (i.e., hypo- or hyperactivity analogous to that of depression or hyperactive disorders in humans). There is evidence that behavior effects may be inherited in subsequent generations, however, the comparative heritability of gut microbial community dynamics after being perturbed is unknown. Further, host organisms biotransform BaP into various metabolites that range in their physiological effects via the AHR2 gene pathway, which also likely modulates assembly of gut microbiota. Thus, we used a zebrafish model to test whether: (1) adult gut microbiome dynamics (i.e., taxonomic diversity and functional capacity) responded to early-life BaP exposure in an AHR2-dependent manner, (2) whether treatments affected the gut microbiota of two subsequent generations, and (3) whether gut microbiome response to BaP exposure and/or AHR2 knockdown was linked to fish behavior. We used a factorial design wherein wild type and AHR2 knockdown embryos were treated with BaP or a sham control, and gut microbiota were sequenced from adult fish at generations F0, F1, and F2, as well as various behavior data collected. We found that BaP exposure perturbed alpha and beta diversity of the gut microbiome in an AHR2-dependent fashion. These effects not only persisted over the lifetime of exposed fish, they also propagated across generations, and in many cases, amplified over generations or skipped a generation. We also identified indicator taxa and gene pathways that were specific to BaP exposure and AHR2 knockdown that we hope to study further in the hopes of understanding how organisms and their microbial communities cope with toxicant exposure, as well as how the AHR2 gene is related to the assembly of gut microbiota. Analysis drawing a connection between fish behavior and gut microbiota is ongoing and forthcoming. Thus, BaP not only represents a disturbance to overall gut microbial community structure and functional traits, but also leads to a successional shift over the course of the zebrafish lifespan and subsequent generations. This points to far-reaching public health consequences that researchers, clinicians, and policy-makers have not considered in the past for this ubiquitous chemical toxicant, and thus requires subsequent study in humans.