Chelsea A Weitekamp1, Allison Kvasnicka2,3, Scott P Keely4, Nichole E Brinkman4, Xia Meng Howey2,3, Shaza Gaballah2,3, Drake Phelps2,3, Tara Catron2,3, Todd Zurlinden3, Emily Wheaton4, Tamara Tal5,6,7. 1. Center for Public Health and Environmental Assessment, US EPA, RTP, NC, USA. 2. Oak Ridge Institute for Science and Education, RTP, NC, USA. 3. , Center for Computational Toxicology and Exposure, US EPA, RTP, NC, USA. 4. Center for Environmental Measurement and Modeling, US EPA, Cincinnati, OH, USA. 5. , Center for Computational Toxicology and Exposure, US EPA, RTP, NC, USA. tamara.tal@ufz.de. 6. Bioanalytical Ecotoxicology Department, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany. tamara.tal@ufz.de. 7. Present Address: Bioanalytical Ecotoxicology Department, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany. tamara.tal@ufz.de.
Abstract
BACKGROUND: Across taxa, animals with depleted intestinal microbiomes show disrupted behavioral phenotypes. Axenic (i.e., microbe-free) mice, zebrafish, and fruit flies exhibit increased locomotor behavior, or hyperactivity. The mechanism through which bacteria interact with host cells to trigger normal neurobehavioral development in larval zebrafish is not well understood. Here, we monoassociated zebrafish with either one of six different zebrafish-associated bacteria, mixtures of these host-associates, or with an environmental bacterial isolate. RESULTS: As predicted, the axenic cohort was hyperactive. Monoassociation with three different host-associated bacterial species, as well as with the mixtures, resulted in control-like locomotor behavior. Monoassociation with one host-associate and the environmental isolate resulted in the hyperactive phenotype characteristic of axenic larvae, while monoassociation with two other host-associated bacteria partially blocked this phenotype. Furthermore, we found an inverse relationship between the total concentration of bacteria per larvae and locomotor behavior. Lastly, in the axenic and associated cohorts, but not in the larvae with complex communities, we detected unexpected bacteria, some of which may be present as facultative predators. CONCLUSIONS: These data support a growing body of evidence that individual species of bacteria can have different effects on host behavior, potentially related to their success at intestinal colonization. Specific to the zebrafish model, our results suggest that differences in the composition of microbes in fish facilities could affect the results of behavioral assays within pharmacological and toxicological studies.
BACKGROUND: Across taxa, animals with depleted intestinal microbiomes show disrupted behavioral phenotypes. Axenic (i.e., microbe-free) mice, zebrafish, and fruit flies exhibit increased locomotor behavior, or hyperactivity. The mechanism through which bacteria interact with host cells to trigger normal neurobehavioral development in larval zebrafish is not well understood. Here, we monoassociated zebrafish with either one of six different zebrafish-associated bacteria, mixtures of these host-associates, or with an environmental bacterial isolate. RESULTS: As predicted, the axenic cohort was hyperactive. Monoassociation with three different host-associated bacterial species, as well as with the mixtures, resulted in control-like locomotor behavior. Monoassociation with one host-associate and the environmental isolate resulted in the hyperactive phenotype characteristic of axenic larvae, while monoassociation with two other host-associated bacteria partially blocked this phenotype. Furthermore, we found an inverse relationship between the total concentration of bacteria per larvae and locomotor behavior. Lastly, in the axenic and associated cohorts, but not in the larvae with complex communities, we detected unexpected bacteria, some of which may be present as facultative predators. CONCLUSIONS: These data support a growing body of evidence that individual species of bacteria can have different effects on host behavior, potentially related to their success at intestinal colonization. Specific to the zebrafish model, our results suggest that differences in the composition of microbes in fish facilities could affect the results of behavioral assays within pharmacological and toxicological studies.
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