Persistent Organic Pollutants Modify Gut Microbiota–Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation

  • Background: Alteration of the gut microbiota through
    diet and environmental contaminants may disturb physiological
    homeostasis, leading to various diseases including obesity and type 2
    diabetes. Since most exposure to environmentally-persistent organic
    pollutants (POPs) occurs through the diet, the host gastrointestinal
    tract and commensal gut microbiota are likely to be exposed to POPs.
    Objectives: We report that
    2,3,7,8-tetrachlorodibenzofuran (TCDF), a persistent environmental
    contaminant, profoundly impacts the gut microbiota and host metabolism
    in an aryl hydrocarbon receptor (AHR)-dependent manner.

    Methods: Six-week-old male wild-type and Ahr-/- mice on the C57BL/6J background were treated with 24 µg/kg TCDF in the diet for five days. 16S rRNA gene sequencing, 1H
    nuclear magnetic resonance (NMR) metabolomics, targeted
    ultra-performance liquid chromatography coupled with triplequadrupole
    mass spectrometry (UPLC-TQMS) and biochemical assays were used to
    determine the microbiota compositions and the physiological and
    metabolic effects of TCDF.

    Results: Dietary TCDF altered the gut microbiota by
    shifting the ratio of Firmicutes to Bacteroidetes. TCDF-treated mouse
    cecal contents were enriched with Butyrivibrio spp., but depleted in
    Oscillobacter spp. in comparison with vehicle-treated mice. These
    changes in the gut microbiota were associated with altered bile acid
    metabolism. Further, dietary TCDF inhibited the farnesoid X receptor
    (FXR) signaling pathway, and triggered significant inflammation and host
    metabolic disorders as a result of activation of bacterial
    fermentation, and altering hepatic lipogenesis, gluconeogenesis and
    glycogenolysis, in an AHR-dependent manner.

    Conclusion: These findings provide new insights into
    the biochemical consequences of TCDF exposure involving the alteration
    of the gut microbiota, modulation of nuclear receptor signaling, and
    disruption of host metabolism.

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