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Host-associated microbiota is required for neurobehavioral development in zebrafish and is targeted by environmental chemicals
Citation:
Tal, T., D. Phelps, N. Brinkman, S. Keely, E. Anneken, D. Hunter, A. Gearhart, D. Betancourt, AND C. Wood. Host-associated microbiota is required for neurobehavioral development in zebrafish and is targeted by environmental chemicals. Eurotox 2017, Bratislava, SLOVAKIA, September 10 - 13, 2017.
Impact/Purpose:
This abstract represents work initiated by a PIP Stage 3 Award and describes data showing that microbes are required for normal neurobehavioral development in zebrafish. In addition, the abstract describes data showing that microbiota can be targeted by chemical exposures during a critical window of brain development.
Description:
Intestinal microbiota may mediate neurodevelopmental behavioral effects of environmental chemicals either by performing biotransformations or serving as a target of chemical exposures. To investigate the consequence of microbial disruption, we evaluated axenic (sterile), conventionally raised, or conventionalized (axenic larvae colonized at 1 day post fertilization (dpf)) zebrafish larvae using a standard locomotor assay consisting of alternating light and dark periods. At 10 dpf, axenic larvae exhibited hyperactivity compared to conventionalized or conventionally raised controls. Impairment of host colonization using antibiotics also caused hyperactivity in conventionally raised larvae. To determine whether microbes are developmentally required, axenic zebrafish were conventionalized on 1, 3, 6, or 9 dpf. Hyperactivity was blocked in larvae conventionalized on 1-6 dpf but not on 9 dpf. Axenic embryos monoassociated with Aeromonas veronii at 1 dpf showed that colonization with a single strain of bacteria was sufficient to block locomotor hyperactivity. Activation of host toll-like receptors by exposure to heat-killed Esherichia coli or Salmonella typhimurium or Pam3CSK4 or Poly(I:C) failed to block locomotor hyperactivity in axenic larvae. To explore the effects of environmental chemicals in our system, axenic, conventionalized, and conventionally raised zebrafish were exposed to environmental chemicals. The effect of chemical exposures on microbiota community structure and locomotor activity will be discussed. These data show that microbial colonization during early life is required for normal neurobehavioral development and support the concept that environmental chemicals, like antibiotics, may exert neurobehavioral effects via impairment of microbial colonization. This abstract does not necessarily reflect EPA policy.