Citation:

Catron, T., S. Keely, N. Brinkman, D. Phelps, E. Anneken, A. Kvasnicka, C. Wood, S. Gaballah, AND T. Tal. Exploring the role of host-associated microbiota as mediators of bisphenol chemical toxicity in zebrafish. SOT, San Antonio, TX, March 11 - 15, 2018.

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. Growing public concern over the safety of BPA has resulted in swift replacement with a suite of alternatives that uniformly lack adequate toxicity data. Because host-associated microbiota play important roles in nervous system development and harbor the ability to bioactivate or detoxify xenobiotics, we hypothesized that developmental exposure to BP compounds may influence microbiota structure and/or cause colonization-dependent neurotoxicity. To test this, a semi-static system was used to expose conventionally colonized zebrafish to BPA, Bisphenol AF (BPAF), Bisphenol B (BPB), Bisphenol F (BPF), or Bisphenol S (BPS). The classic estrogen receptor agonist 17beta-estradiol (E2) was used as a positive control. At 10 days post fertilization (dpf) larvae were assessed for mortality, and a range of potencies was observed: BPAF > E2 > BPB > BPA > BPF > BPS. To evaluate potential chemical-dependent shifts in microbiota structure in 10 dpf conventionally colonized zebrafish, 16S rRNA gene sequencing was performed. Concentration-dependent disruption of microbiota was observed with exposure to BPA, BPF, and BPS, while exposure to E2, BPB, and BPAF, the most overtly toxic compounds, did not alter microbiota structure. To assess whether neurobehavioral toxicity was mediated by microbiota, we exposed three cohorts of zebrafish to all six compounds: conventionally colonized, 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 behavioral assay. Hypoactivity was observed in colonized larvae only with E2 exposure. While some BP compounds caused neurobehavioral toxicity in one or more cohorts, the effect was not colonization-dependent. Overall, these data demonstrate that the least overtly toxic BP compounds cause the most significant alterations in microbiota structure in 10 dpf zebrafish. These differential chemical effects suggest that current hazard identification strategies have the potential to misestimate risk if chemical-microbiota interactions are not considered. This abstract does not necessarily reflect EPA policy.

Record Details: