Exploring host-associated microbiota as mediators of neurobehavioral toxicity in zebrafish larvae developmentaly exposed to triclosan

摘要

Growing evidence indicates that host-associated microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals; however, current risk assessment methods do not consider interactions between microbiota and chemical toxicity. We previously reported that microbial colonization is required for normal neurobehavioral development in zebrafish. We therefore hypothesized that neurobehavioral toxicity may be mediated by altered microbial colonization during development. We explored differences in swimming behavior, microbial community structure, and chemical metabolism in axenic (microbe-free) and conventionally colonized zebrafish larvae that were exposed to the antimicrobial triclosan (0.1-0.3 μM) or vehicle (0.4% DMSO) on $16, 7, 8, and 9 days post fertilization (dpf). At 10 dpf, neurobehavioral function was assessed. Triclosan exposure had no effect on locomotor activity in axenic larvae. In comparison, locomotor hypoactivity was observed in conventionally colonized larvae exposed to 0.3 uM, but not 0.1 uM triclosan. Also on 10 dpf, triclosan exposure triggered concentration-dependent shifts in microbial community structure. To understand the temporal dynamics of triclosan-induced hypoactivity, conventionally colonized larvae were exposed to 0.3 μM triclosan in four scenarios: 1 dpf; 1 and 6 dpf; 1 and 9 dpf; or 1, 6, 7, 8, and 9 dpf. Triclosan exposure only caused hypoactivity at 10 dpf in larvae exposed on 1 and 9 dpf or 1, 6, 7, 8, and 9 dpf. As expected, these two groups contained elevated concentrations of triclosan (ng/larva) at 10 dpf compared to larvae exposed to triclosan on 1 dpf as measured by high resolution mass spectrometry. Ultimately, this study will serve as a test case to apply non-targeted chemical analyses to reveal unique biotransformation products in axenic and conventionally colonized zebrafish exposed to triclosan during development. In summary, these data suggest that triclosan may exert behavioral effects via dysregulation of microbial colonization during development. This abstract does not necessarily reflect EPA policy.