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Nontarget analysis reveals gut microbiome-dependent differences in the fecal PCB metabolite profiles of germ-free and conventional mice
Journal article   Peer reviewed

Nontarget analysis reveals gut microbiome-dependent differences in the fecal PCB metabolite profiles of germ-free and conventional mice

Xueshu Li, Yanna Liu, Jonathan W Martin, Julia Yue Cui and Hans-Joachim Lehmler
Environmental pollution (1987), Vol.268, 115726
01/2021
DOI: 10.1016/j.envpol.2020.115726
PMCID: PMC7746632
PMID: 33032095
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https://www.ncbi.nlm.nih.gov/pmc/articles/7746632View
Open Access

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Abstract

Mammalian polychlorinated biphenyl (PCB) metabolism has not been systematically explored with nontarget high-resolution mass spectrometry (Nt-HRMS). Here we investigated the importance of the gut microbiome in PCB biotransformation by Nt-HRMS analysis of feces from conventional (CV) and germ-free (GF) adult female mice exposed to a single oral dose of an environmental PCB mixture (6 mg/kg or 30 mg/kg in corn oil). Feces were collected for 24 h after PCB administration, PCB metabolites were extracted from pooled samples, and the extracts were analyzed by Nt-HRMS. Twelve classes of PCB metabolites were detected in the feces from CV mice, including PCB sulfates, hydroxylated PCB sulfates (OH-PCB sulfates), PCB sulfonates, and hydroxylated methyl sulfone PCBs (OH-MeSO2-PCBs) reported previously. We also observed eight additional PCB metabolite classes that were tentatively identified as hydroxylated PCBs (OH-PCBs), dihydroxylated PCBs (DiOH-PCBs), monomethoxylated dihydroxylated PCBs (MeO-OH-PCBs), methoxylated PCB sulfates (MeO-PCB sulfates), mono-to tetra-hydroxylated PCB quinones ((OH)x-quinones, x = 1–4), and hydroxylated polychlorinated benzofurans (OH-PCDF). Most metabolite classes were also detected in the feces from GF mice, except for MeO-OH-PCBs, OH-MeSO2-PCBs, and OH-PCDFs. Semi-quantitative analyses demonstrate that relative PCB metabolite levels increased with increasing dose and were higher in CV than GF mice, except for PCB sulfates and MeO-PCB sulfates, which were higher in GF mice. These findings demonstrate that the gut microbiome plays a direct or indirect role in the absorption, distribution, metabolism, or excretion of PCB metabolites, which in turn may affect toxic outcomes following PCB exposure. [Display omitted] •PCB metabolites were identified with non-target high-resolution mass spectrometry.•Feces from mice exposed to a PCB mixture contained twelve PCB metabolite classes.•PCB metabolite levels were typically higher in conventional than germ-free mice.•Levels of some sulfated metabolites were higher in germ-free than conventional mice.•Some PCB metabolite classes were not detected in conventional mice. Female conventional and germ-free mice eliminate up to twelve classes of PCB metabolites with the feces following oral exposure to an environmental PCB mixture in a dose- and enterotype-dependent manner.
 Mus musculus Feces Nontarget high-resolution mass spectrometry PCB metabolites Enterotype Synthesis Core University of Washington collaboration

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