Using Zebrafish to Investigate Interactions Between Xenobiotics and Microbiota

Purpose of Review Humans underwent coevolution with microbes that engage in a range of mutually beneficial functions. The intestinal microbiome consists of trillions of microorganisms and their genes and encoded functions that colonize the host gastrointestinal tract. There is growing interest in understanding the mechanisms by which microbiota interact with xenobiotics to affect host toxicity outcomes. This review will focus on exploring recent evidence that supports interactions between xenobiotics and host-associated microbes, specifically in the zebrafish model. The benefits and shortcomings of the zebrafish model in the context of chemical-microbiome interactions and major knowledge gaps will also be discussed. Recent Findings A multitude of studies in larval or adult zebrafish demonstrate the utility of the model system to describe dysbiosis, characterized by alterations in the community structure of host-associated microbiota, following exposure to drugs or environmental chemicals. Recent evidence obtained in the zebrafish model supports a toxicokinetic interaction between chemicals and microbiota in which intestinal microorganisms bioactivate or detoxify xenobiotics. Fewer studies support the toxicodynamic theory in which xenobiotic-induced dysbiosis subsequently triggers adverse outcomes in the host organism. Summary Zebrafish is a vertebrate experimental model widely used for toxicological research in the context of hazard identification, chemical prioritization, and mode-of-action elucidation. Zebrafish is also a powerful model for microbiome research because it is relatively straightforward to control colonization status during early development via the generation, maintenance, and conventionalization of axenic animals. Larval zebrafish can therefore be uniquely leveraged to illuminate toxicokinetic and toxicodynamic implications of host-associated microbiota on chemical exposures.