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. Because 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 examined the effect of 2,3,7,8-tetrachlorodibenzofuran (TCDF), a persistent environmental contaminant, on gut microbiota and host metabolism, and we examined correlations between gut microbiota composition and signaling pathways.
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 5 days. We used 16S rRNA gene sequencing, 1H nuclear magnetic resonance (NMR) metabolomics, targeted ultra-performance liquid chromatography coupled with triplequadrupole mass spectrometry, and biochemical assays 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. compared 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, triggered significant inflammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered 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.
1Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, USA; 2Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, CAS, Wuhan, China; 3Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA; 4Bioinformatics Consulting Center, and 5Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA
Recommended Citation:
Limin Zhang,1,2 Robert G. Nichols,et al. Persistent Organic Pollutants Modify Gut Microbiota–Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation[J]. Environmental Health Perspectives,2015-01-01,Volume 123(Issue 7):679