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Host-associated microbiota modifies the toxicokinetics of environmental chemicals
Citation:
Tal, T. Host-associated microbiota modifies the toxicokinetics of environmental chemicals. Zebrafish Training Workshop, Morgontown, WV, April 09, 2018.
Impact/Purpose:
Host-associated microbes or microbiota harbor the capacity to activate or detoxify environmental chemicals. This work shows that exposure to the antimicrobial agent triclosan selects for triclosan resistant bacteria. These microbes function to increase levels of parent triclosan in the host zebrafish and biotransform triclosan into triclosan sulfate, a compound with an unknown toxicity profile. These data support the concept that microbiota modifies the toxicokinetics of xenobiotic exposures.
Description:
Host-associated microbiota are known to biotransform drugs and some environmental chemicals like arsenic and polycyclic aromatic hydrocarbons. However, the metabolic capacity of microbiota treated with anti-microbial agents has not been assessed. Here, we exposed zebrafish with altered microbial colonization statuses to the antimicrobial agent triclosan. Conventionally colonized (CC), microbe-free axenic (AX), or axenic zebrafish colonized on day 1 (AC1) were exposed to 0.16-0.3 uM triclosan or 0.1% DMSO on 1, 6, 7, 8, and 9 days post fertilization (dpf). On 6 dpf and 10 dpf, host-associated microbiota community structure was assessed by 16S rRNA sequencing. To measure parent compound, targeted analytical chemistry was performed at 6 dpf and 10 dpf on media and zebrafish larvae obtained from flasks used for 16S-based sequencing. Chemical metabolism was additionally assessed using non-targeted analysis (NTA). At 10 dpf, triclosan exposure in CC or AC1 groups selected for resistant bacterial taxa that are predicted to biotransform triclosan. Also at 10 dpf, colonized zebrafish contained 2.5-3 fold more triclosan relative to microbe-free AX larvae. NTA was used to identify chemical biotransformations performed by host-associated microbiota. Relative to microbe-free larvae, 23 chemical features were elevated in both cohorts of colonized larvae, including parent triclosan and triclosan sulfate. Taken together, these data show that triclosan exposure selects for resistant microbes that harbor the capacity to biotransform triclosan into chemical metabolites with unknown toxicity profiles. More broadly, these data support the concept that microbiota modifies the toxicokinetics of xenobiotic exposures.