PMID- 25768209
OWN - NLM
STAT- MEDLINE
DCOM- 20160511
LR  - 20240516
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 123
IP  - 7
DP  - 2015 Jul
TI  - Persistent Organic Pollutants Modify Gut Microbiota-Host Metabolic Homeostasis in 
      Mice Through Aryl Hydrocarbon Receptor Activation.
PG  - 679-88
LID - 10.1289/ehp.1409055 [doi]
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 
      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 mug/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.
FAU - Zhang, Limin
AU  - Zhang L
AD  - Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and 
      Biomedical Sciences, The Pennsylvania State University, University Park, 
      Pennsylvania, USA.
FAU - Nichols, Robert G
AU  - Nichols RG
FAU - Correll, Jared
AU  - Correll J
FAU - Murray, Iain A
AU  - Murray IA
FAU - Tanaka, Naoki
AU  - Tanaka N
FAU - Smith, Philip B
AU  - Smith PB
FAU - Hubbard, Troy D
AU  - Hubbard TD
FAU - Sebastian, Aswathy
AU  - Sebastian A
FAU - Albert, Istvan
AU  - Albert I
FAU - Hatzakis, Emmanuel
AU  - Hatzakis E
FAU - Gonzalez, Frank J
AU  - Gonzalez FJ
FAU - Perdew, Gary H
AU  - Perdew GH
FAU - Patterson, Andrew D
AU  - Patterson AD
LA  - eng
GR  - ES019964/ES/NIEHS NIH HHS/United States
GR  - R01 ES019964/ES/NIEHS NIH HHS/United States
GR  - Intramural NIH HHS/United States
GR  - ES004869/ES/NIEHS NIH HHS/United States
GR  - R01 ES004869/ES/NIEHS NIH HHS/United States
GR  - R01 ES022186/ES/NIEHS NIH HHS/United States
GR  - ES022186/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20150313
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Benzofurans)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Environmental Pollutants)
RN  - 0 (RNA, Ribosomal, 16S)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0C5V0MRU6P (farnesoid X-activated receptor)
RN  - XZJ41GQI5D (2,3,7,8-tetrachlorodibenzofuran)
SB  - IM
CIN - Environ Health Perspect. 2015 Jul;123(7):A187. PMID: 26131758
MH  - Animals
MH  - Benzofurans/*toxicity
MH  - Bile Acids and Salts/metabolism
MH  - Diet
MH  - Environmental Pollutants/*toxicity
MH  - Gastrointestinal Microbiome/*drug effects/genetics
MH  - Gastrointestinal Tract/*microbiology
MH  - Homeostasis
MH  - Liver/*drug effects/metabolism
MH  - Male
MH  - Metabolomics
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microbiota/*drug effects/genetics
MH  - RNA, Ribosomal, 16S/metabolism
MH  - Receptors, Aryl Hydrocarbon/genetics/*metabolism
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Signal Transduction
PMC - PMC4492271
COIS- The authors declare they have no actual or potential competing financial 
      interests.
EDAT- 2015/03/15 06:00
MHDA- 2016/05/12 06:00
PMCR- 2015/07/01
CRDT- 2015/03/14 06:00
PHST- 2014/08/07 00:00 [received]
PHST- 2015/03/09 00:00 [accepted]
PHST- 2015/03/14 06:00 [entrez]
PHST- 2015/03/15 06:00 [pubmed]
PHST- 2016/05/12 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - ehp.1409055 [pii]
AID - 10.1289/ehp.1409055 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2015 Jul;123(7):679-88. doi: 10.1289/ehp.1409055. Epub 
      2015 Mar 13.