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.