Abstract: Polychlorinated biphenyls (PCBs) are neurotoxic hazardous materials that may cause toxicity via the gut-liver-brain axis. This study investigated PCB × microbiome interactions in adult female mice exposed orally to an environmental PCB mixture. Female mice (6-week-old) were exposed daily for 7 weeks to peanut butter containing 0, 0.1, 1, or 6 mg/kg/day of PCBs. Twenty hours after the final exposure, the cecal content was collected to characterize the microbiome composition and predicted function. PCB and its metabolites in feces were analyzed using gas chromatography-tandem mass spectrometry (GC-MS/MS), while cecal content was assessed with liquid chromatography-high resolution mass spectrometry (LC-HRMS). PCB exposure influenced the abundance of microbial taxa and predicted functions within the cecal content. Complex PCB and metabolite mixtures were detected in the gastrointestinal tract. Network analysis revealed associations between specific parent PCBs and metabolites with changes in the abundance of bacteria in the gastrointestinal tract. These findings demonstrate that individual PCBs and their metabolites significantly influence the abundance of specific bacteria in the gastrointestinal tract following oral PCB exposure. These findings inform further research targeting the microbiome to attenuate the adverse health outcomes of PCB exposure.
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