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Host Developmental Toxicity of BPA and BPA Alternatives Is Inversely Related to Microbiota Disruption in Zebrafish
Citation:
Catron, T., S. Keely, N. Brinkman, T. Zurlinden, C. Wood, J. Wright, D. Phelps, E. Wheaton, A. Kvasnicka, S. Gaballah, R. Lamendella, AND T. Tal. Host Developmental Toxicity of BPA and BPA Alternatives Is Inversely Related to Microbiota Disruption in Zebrafish. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 167(2):468-483, (2019). https://doi.org/10.1093/toxsci/kfy261
Impact/Purpose:
Intestinal microbes are thought to play important roles in early development. It has been proposed that microbiota can bioactivate or detoxify environmental chemicals and mediate health effects of chemical exposure. Bisphenol A is a widespread environmental contaminant found in a variety of consumer products. Due to concerns over toxicity, bisphenol A has been replaced with structurally similar alternative chemicals. Using zebrafish as a model, this work shows that exposure to bisphenol A, bisphenol F, and bisphenol S, the three chemicals identified to be the least toxic to the developing zebrafish, results in significant disruption of microbial community structure and function. Exposure to bisphenol B and bisphenol AF, the two most developmentally toxic chemicals, does not alter microbiota structure. Exposure to bisphenol A and alternatives does not alter locomotor activity, an endpoint used to assess neurotoxicity. To our knowledge, this is the first study to show that microbiota disruption is, in general, inversely related to host developmental toxicity and estrogenic activity of bisphenol A and alternatives. These findings indicate that exposure to bisphenol A and certain structurally similar alternatives alter microbial communities during early life and demonstrate novel chemical-microbe interactions that may add context to current hazard identification strategies.
Description:
Host-associated microbiota can biotransform xenobiotics, mediate health effects of chemical exposure, and play important roles in early development. Bisphenol A (BPA) is a widespread environmental chemical that has been associated with adverse endocrine and neurodevelopmental effects, some of which may be mediated by microbiota. Growing public concern over the safety of BPA has resulted in its replacement with structurally similar alternatives. In this study, we evaluated whether BPA and BPA alternatives alter microbiota and modulate secondary adverse behavioral effects in zebrafish. Zebrafish were developmentally exposed to BPA, Bisphenol AF (BPAF), Bisphenol B (BPB), Bisphenol F (BPF), or Bisphenol S (BPS). At 10 days post fertilization (dpf), toxicity assessments were completed and 16S rRNA gene sequencing was performed to evaluate potential chemical-dependent shifts in microbial community structure and predicted function. A standard light/dark behavioral assay was used to assess locomotor activity. Based on developmental toxicity assessments at 10 dpf, a range of potencies was observed: BPAF > BPB > BPF ∼ BPA > BPS. Analysis of 16S rRNA gene sequencing data showed significant concentration-dependent disruption of microbial community structure and enrichment of putative microbial functions with exposure to BPS, BPA, or BPF, but not BPB or BPAF. Interestingly, microbial disruption was inversely related to host developmental toxicity and estrogenicity. Exposure to BP analogues did not cause behavioral effects at 10 dpf. Our findings indicate that some BP analogues disrupt host microbiota early in life and demonstrate novel chemical-microbiota interactions that may add important context to current hazard identification strategies.
URLs/Downloads:
DOI: Host Developmental Toxicity of BPA and BPA Alternatives Is Inversely Related to Microbiota Disruption in Zebrafish