You are here:
Exploring the Role of Host-associated Microbiota as Mediators of Bisphenol Chemical Toxicity in Zebrafish..
Citation:
Catron, T., D. Phelps, S. Keely, N. Brinkman, E. Anneken, A. Kvasnicka, C. Wood, AND T. Tal. Exploring the Role of Host-associated Microbiota as Mediators of Bisphenol Chemical Toxicity in Zebrafish.. NC GEMS, Durham, NC, November 07, 2017.
Impact/Purpose:
Intestinal microbes are thought to play important roles in development of the nervous system. It has been proposed that microbiota, through bioactivation or detoxification, may mediate the developmental toxicity of environmental chemicals. This work shows that exposure to bisphenol A, bisphenol F, and bisphenol S, the three least overtly toxic chemicals identified in our study, results in significant concentration-dependent disruption of microbiota structure. Exposure to 17 beta-estradiol, bisphenol B, and bisphenol AF, the three most overtly toxic chemicals, does not alter microbiota structure. Furthermore, exposure to 17beta-estradiol, a potent estrogen receptor agonist, causes neurotoxicity only in zebrafish with microbes. Exposure to bisphenol A and replacement compounds did not alter neurobehavior in zebrafish when microbes were either present or absent. The differential chemical effects observed here suggest that current hazard identification strategies have the potential to misestimate risk if interactions between chemicals and microbiota are not considered.
Description:
Exposure to Bisphenol A (BPA), a widespread environmental contaminant, has been associated with adverse endocrine and neurodevelopmental effects. Because host-associated microbiota play important roles in neurodevelopment and may bioactivate or detoxify xenobiotics, we hypothesized that developmental exposure to bisphenol compounds may influence microbiota community structure leading to colonization-dependent neurotoxicity. Conventionally colonized (CC) zebrafish were exposed to BPA, Bisphenol AF (BPAF), Bisphenol B (BPB), Bisphenol F (BPF), or Bisphenol S (BPS). The classic estrogen receptor agonist 17beta-estradiol (E2) served as a positive control. At 10 days post fertilization (dpf) larvae were assessed for mortality and a range of potencies were observed: BPAF > E2 > BPB > BPA > BPF > BPS. To evaluate potential chemical-dependent shifts in microbiota structure, 16S rRNA gene sequencing was performed. Concentration-dependent microbiota disruption was observed with BPA, BPF, and BPS exposure. BPAF, BPB and E2 exposure did not alter microbiota. These data demonstrate that the least overtly toxic bisphenol compounds cause the most significant alterations in microbiota structure. To determine if neurobehavioral toxicity was mediated by microbiota, three zebrafish cohorts were exposed to each chemical: CC, axenic (microbe-free), and axenic colonized with zebrafish facility water at 1 dpf. At 10 dpf, neurobehavioral effects were assessed using an established light/dark assay. Colonization-dependent hypoactivity was observed only with E2 exposure. While some BP compounds caused neurotoxicity, the effect was not colonization-dependent. These differential effects suggest that current hazard identification strategies may misestimate risk if chemical-microbiota interactions are not considered. This abstract does not necessarily reflect EPA policy.