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Microbiota modifies chemical toxicity
Citation:
Tal, T. Microbiota modifies chemical toxicity. U.C. Berkeley Superfund Meeting, Berkeley, CA, January 30, 2018.
Impact/Purpose:
Intestinal microbes play important roles in development. It has been proposed that microbiota, through bioactivation or detoxification, may mediate the developmental toxicity of environmental chemicals. This work describes an experimental system comprised of colonized and microbe-free zebrafish. Using this system, we show that microbes are required for neurobehavioral development. This work also shows that exposure to bisphenol A, bisphenol F, and bisphenol S, the three least overtly toxic bisphenol chemicals identified in our study, results in significant concentration-dependent disruption of microbiota structure. In a triclosan case study, we also show that microbes function to increase uptake of the parent chemical. Collectively, this work supports the concept that microbiota modify the toxicokinetics and toxicodynamics of environmental chemicals.
Description:
Microbiota consists of all the bacteria, viruses, and fungi external to the body. These microbes colonize host organisms at birth and the association continues throughout life. Microbes are necessary for development of host organs and systems, including the nervous system. Intestinal microbes can influence the developing nervous system directly via the vagal nerve and indirectly via the secretion of soluble factors that enter the host circulatory system, penetrate the blood brain barrier, and exert direct effects on brain development and function. This so-called microbiota-gut-brain axis is increasingly suspected to be disrupted by exposure to environmental chemicals. This disruption may occur by two mechanisms. One, chemical exposures harbor the ability to disrupt microbial colonization. Two, microbial proteins may biotransform environmental chemicals to change chemical potency. We have developed and evaluated an experimental system comprised of colonized and microbe-free zebrafish to test the hypothesis that host-associated microbiota modifies the toxicity of environmental chemicals. We used locomotor activity in response to light stimuli as a functional readout of brain development in colonized and microbe-free zebrafish. We show that zebrafish that lack microbes are hyperactive relatived to colonized controls and that exposure of colonized zebrafish to antibiotics also causes hyperactivity. To explore the effects of environmental chemicals in our system, colonized and microbe-free zebrafish were exposed to the antimicrobial agents triclosan or triclocarban or to bisphenol A or replacement chemicals bisphenol AF, bisphenol B, bisphenol F, or biphenol S. Microbe-dependent effects on locomotor activity, chemical metabolism, and microbiota community structure will be discussed. This abstract does not necessarily reflect EPA policy.