Polybrominated diphenyl ethers and gut microbiome modulate metabolic syndrome-related aqueous metabolites in mice

David K. Scoville, Cindy Yanfei Li, Dongfang Wang, Joseph L. Dempsey, Daniel Raftery, Sridhar Mani, Haiwei Gu, Julia Yue Cui

Research output: Contribution to journalArticle

Abstract

Polybrominated diphenyl ethers (PBDEs) are persistent environmental toxicants associated with increased risk for metabolic syndrome. Intermediary metabolism is influenced by the intestinal microbiome. To test the hypothesis that PBDEs reduce hostbeneficial intermediary metabolites in an intestinal microbiome- dependent manner, 9-week old male conventional (CV) and germfree (GF) C57BL/6 mice were orally gavaged once daily with vehicle, BDE-47, or BDE-99 (100 mmol/kg) for 4 days. Intestinal microbiome (16S rDNA sequencing), liver transcriptome (RNA-Seq), and intermediary metabolites in serum, liver, as well as small and large intestinal contents (SIC and LIC; LC-MS) were examined. Changes in intermediary metabolite abundances in serum, liver, and SIC, were observed under basal conditions (CV vs. GF mice) and by PBDE exposure. PBDEs altered the largest number of metabolites in the LIC; most were regulated by PBDEs in GF conditions. Importantly, intestinal microbiome was necessary for PBDE-mediated decreases in branched-chain and aromatic amino acid metabolites, including 3-indolepropionic acid, a tryptophan metabolite recently shown to be protective against inflammation and diabetes. Gene-metabolite networks revealed a positive association between the hepatic glycan synthesis gene a-1,6-mannosyltransferase (Alg12) mRNA and mannose, which are important for protein glycosylation. Glycome changes have been observed in patients with metabolic syndrome. In LIC of CV mice, 23 bacterial taxa were regulated by PBDEs. Correlations of certain taxa with distinct serum metabolites further highlight a modulatory role of the microbiome in mediating PBDE effects. In summary, PBDEs impact intermediary metabolism in an intestinal microbiome-dependent manner, suggesting that dysbiosis may contribute to PBDE-mediated toxicities that include metabolic syndrome.

Original languageEnglish (US)
Pages (from-to)928-940
Number of pages13
JournalDrug Metabolism and Disposition
Volume47
Issue number8
DOIs
StatePublished - Jan 1 2019

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Halogenated Diphenyl Ethers
Liver
Mannosyltransferases
Serum
Dysbiosis
Gastrointestinal Microbiome
Branched Chain Amino Acids
Aromatic Amino Acids
Gastrointestinal Contents
Gene Regulatory Networks
Microbiota
Mannose
Ribosomal DNA
Glycosylation
Inbred C57BL Mouse
Transcriptome
Tryptophan
Polysaccharides

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Polybrominated diphenyl ethers and gut microbiome modulate metabolic syndrome-related aqueous metabolites in mice. / Scoville, David K.; Li, Cindy Yanfei; Wang, Dongfang; Dempsey, Joseph L.; Raftery, Daniel; Mani, Sridhar; Gu, Haiwei; Cui, Julia Yue.

In: Drug Metabolism and Disposition, Vol. 47, No. 8, 01.01.2019, p. 928-940.

Research output: Contribution to journalArticle

Scoville, David K. ; Li, Cindy Yanfei ; Wang, Dongfang ; Dempsey, Joseph L. ; Raftery, Daniel ; Mani, Sridhar ; Gu, Haiwei ; Cui, Julia Yue. / Polybrominated diphenyl ethers and gut microbiome modulate metabolic syndrome-related aqueous metabolites in mice. In: Drug Metabolism and Disposition. 2019 ; Vol. 47, No. 8. pp. 928-940.
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