Exploring interactions between xenobiotics, microbiota, and neurotoxicity in zebrafish

•Zebrafish is a powerful in vivo system for the investigation of chemical exposures, microorganisms, and host neurotoxicological outcomes.•Xenobiotic exposure can cause dysbiosis and microbiota can biotrans form environmental chemicals into products with unknown toxicity profiles.•It is less clear whether dysbiosis or toxicokinetic interactions lead to host toxicity (i.e. Toxicodynamic interactions).•Comparison of colonized and axenic (i.e. microbe-free) zebrafish can reveal mechanisms by which the microbiome modifies the developmental neurotoxicity of environmental chemicals. Susceptibility to xenobiotic exposures is variable. One factor that might account for this is the microbiome, which encompasses all microorganisms, their encoded genes, and associated functions that colonize a host organism. Microbiota harbor the capacity to affect the toxicokinetics and toxicodynamics of xenobiotic exposures. The neurotoxicological effects of environmental chemicals may be modified by intestinal microbes via the microbiota-gut-brain axis. This is a complex, bi-directional signaling pathway between intestinal microbes and the host nervous system. As a model organism, zebrafish are extremely well-placed to illuminate mechanisms by which microbiota modify the developmental neurotoxicity of environmental chemicals. The goal of this review article is to examine the microbiota-gut-brain axis in a toxicological context, specifically focusing on the strengths and weaknesses of the zebrafish model for the investigation of interactions between xenobiotic agents and host-associated microbes. Previous studies describing the relationship between intestinal microbes and host neurodevelopment will be discussed. From a neurotoxicological perspective, studies utilizing zebrafish to assess links between neurotoxicological outcomes and the microbiome are emphasized. Overall, there are major gaps in our understanding the mechanisms by which microbiota interact with xenobiotics to cause or modify host neurotoxicity. In this review, we demonstrate that zebrafish are an ideal model system for studying the complex relationship between chemical exposures, microorganisms, and host neurotoxicological outcomes.