TY - JOUR
T1 - Persistent organic pollutants modify gut microbiota–host metabolic homeostasis in mice through aryl hydrocarbon receptor activation
AU - Zhang, Limin
AU - Nichols, Robert G.
AU - Correll, Jared
AU - Murray, Iain A.
AU - Tanaka, Naoki
AU - Smith, Philip B.
AU - Hubbard, Troy D.
AU - Sebastian, Aswathy
AU - Albert, Istvan
AU - Hatzakis, Emmanuel
AU - Gonzalez, Frank J.
AU - Perdew, Gary H.
AU - Patterson, Andrew D.
N1 - Publisher Copyright:
© 2015, Public Health Services, US Dept of Health and Human Services. All Rights Reserved.
PY - 2015/7/6
Y1 - 2015/7/6
N2 - 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 gastro intestinal tract and commensal gut microbiota are likely to be exposed to POPs. oBjectives: We examined the effect of 2,3,7,8-tetrachloro dibenzofuran (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 infammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipo genesis, gluco neo genesis, and glyco genolysis 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.
AB - 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 gastro intestinal tract and commensal gut microbiota are likely to be exposed to POPs. oBjectives: We examined the effect of 2,3,7,8-tetrachloro dibenzofuran (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 infammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipo genesis, gluco neo genesis, and glyco genolysis 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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U2 - 10.1289/ehp.1409055
DO - 10.1289/ehp.1409055
M3 - Article
C2 - 25768209
AN - SCOPUS:84936159079
SN - 0091-6765
VL - 123
SP - 679
EP - 688
JO - Environmental health perspectives
JF - Environmental health perspectives
IS - 7
ER -