PBDEs altered gut microbiome and bile acid homeostasis in male C57BL/6 mice

Cindy Yanfei Li, Joseph L. Dempsey, Dongfang Wang, Soo Wan Lee, Kris M. Weigel, Qiang Fei, Deepak Kumar Bhatt, Bhagwat Prasad, Daniel Raftery, Haiwei Gu, Julia Yue Cui

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothesis that PBDEs cause dysbiosis and aberrant regulation of BA homeostasis. Nine-week-old male C57BL/6 conventional (CV) and germ-free (GF) mice were orally gavaged with corn oil (10 mg/kg), BDE-47 (100 µmol/kg), or BDE-99 (100 µmol/kg) once daily for 4 days (n = 3–5/group). Gut microbiome was characterized using 16S rRNA sequencing of the large intestinal content in CV mice. Both BDE-47 and BDE-99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. Both PBDE congeners increased Akkermansia muciniphila and Erysipelotrichaceae Allobaculum spp., which have been reported to have anti-inflammatory and antiobesity functions. Targeted metabolomics of 56 BAs was conducted in serum, liver, and small and large intestinal content of CV and GF mice. BDE-99 increased many unconjugated BAs in multiple biocompartments in a gut microbiota-dependent manner. This correlated with an increase in microbial 7α-dehydroxylation enzymes for secondary BA synthesis and increased expression of host intestinal transporters for BA absorption. Targeted proteomics showed that PBDEs downregulated host BA-synthesizing enzymes and transporters in livers of CV but not GF mice. In conclusion, there is a novel interaction between PBDEs and the endogenous BA-signaling through modification of the “gut-liver axis”.

Original languageEnglish (US)
Pages (from-to)1226-1240
Number of pages15
JournalDrug Metabolism and Disposition
Volume46
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Halogenated Diphenyl Ethers
Bile Acids and Salts
Inbred C57BL Mouse
Homeostasis
Gastrointestinal Contents
Liver
Dysbiosis
Metabolomics
Corn Oil
Gastrointestinal Microbiome
Xenobiotics
Enzymes
Biotransformation
Proteomics
Anti-Inflammatory Agents
Down-Regulation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Li, C. Y., Dempsey, J. L., Wang, D., Lee, S. W., Weigel, K. M., Fei, Q., ... Cui, J. Y. (2018). PBDEs altered gut microbiome and bile acid homeostasis in male C57BL/6 mice. Drug Metabolism and Disposition, 46(8), 1226-1240. https://doi.org/10.1124/dmd.118.081547

PBDEs altered gut microbiome and bile acid homeostasis in male C57BL/6 mice. / Li, Cindy Yanfei; Dempsey, Joseph L.; Wang, Dongfang; Lee, Soo Wan; Weigel, Kris M.; Fei, Qiang; Bhatt, Deepak Kumar; Prasad, Bhagwat; Raftery, Daniel; Gu, Haiwei; Cui, Julia Yue.

In: Drug Metabolism and Disposition, Vol. 46, No. 8, 01.08.2018, p. 1226-1240.

Research output: Contribution to journalArticle

Li, CY, Dempsey, JL, Wang, D, Lee, SW, Weigel, KM, Fei, Q, Bhatt, DK, Prasad, B, Raftery, D, Gu, H & Cui, JY 2018, 'PBDEs altered gut microbiome and bile acid homeostasis in male C57BL/6 mice', Drug Metabolism and Disposition, vol. 46, no. 8, pp. 1226-1240. https://doi.org/10.1124/dmd.118.081547
Li, Cindy Yanfei ; Dempsey, Joseph L. ; Wang, Dongfang ; Lee, Soo Wan ; Weigel, Kris M. ; Fei, Qiang ; Bhatt, Deepak Kumar ; Prasad, Bhagwat ; Raftery, Daniel ; Gu, Haiwei ; Cui, Julia Yue. / PBDEs altered gut microbiome and bile acid homeostasis in male C57BL/6 mice. In: Drug Metabolism and Disposition. 2018 ; Vol. 46, No. 8. pp. 1226-1240.
@article{16644899b049423597e8d2b0e599acbd,
title = "PBDEs altered gut microbiome and bile acid homeostasis in male C57BL/6 mice",
abstract = "Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothesis that PBDEs cause dysbiosis and aberrant regulation of BA homeostasis. Nine-week-old male C57BL/6 conventional (CV) and germ-free (GF) mice were orally gavaged with corn oil (10 mg/kg), BDE-47 (100 µmol/kg), or BDE-99 (100 µmol/kg) once daily for 4 days (n = 3–5/group). Gut microbiome was characterized using 16S rRNA sequencing of the large intestinal content in CV mice. Both BDE-47 and BDE-99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. Both PBDE congeners increased Akkermansia muciniphila and Erysipelotrichaceae Allobaculum spp., which have been reported to have anti-inflammatory and antiobesity functions. Targeted metabolomics of 56 BAs was conducted in serum, liver, and small and large intestinal content of CV and GF mice. BDE-99 increased many unconjugated BAs in multiple biocompartments in a gut microbiota-dependent manner. This correlated with an increase in microbial 7α-dehydroxylation enzymes for secondary BA synthesis and increased expression of host intestinal transporters for BA absorption. Targeted proteomics showed that PBDEs downregulated host BA-synthesizing enzymes and transporters in livers of CV but not GF mice. In conclusion, there is a novel interaction between PBDEs and the endogenous BA-signaling through modification of the “gut-liver axis”.",
author = "Li, {Cindy Yanfei} and Dempsey, {Joseph L.} and Dongfang Wang and Lee, {Soo Wan} and Weigel, {Kris M.} and Qiang Fei and Bhatt, {Deepak Kumar} and Bhagwat Prasad and Daniel Raftery and Haiwei Gu and Cui, {Julia Yue}",
year = "2018",
month = "8",
day = "1",
doi = "10.1124/dmd.118.081547",
language = "English (US)",
volume = "46",
pages = "1226--1240",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "8",

}

TY - JOUR

T1 - PBDEs altered gut microbiome and bile acid homeostasis in male C57BL/6 mice

AU - Li, Cindy Yanfei

AU - Dempsey, Joseph L.

AU - Wang, Dongfang

AU - Lee, Soo Wan

AU - Weigel, Kris M.

AU - Fei, Qiang

AU - Bhatt, Deepak Kumar

AU - Prasad, Bhagwat

AU - Raftery, Daniel

AU - Gu, Haiwei

AU - Cui, Julia Yue

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothesis that PBDEs cause dysbiosis and aberrant regulation of BA homeostasis. Nine-week-old male C57BL/6 conventional (CV) and germ-free (GF) mice were orally gavaged with corn oil (10 mg/kg), BDE-47 (100 µmol/kg), or BDE-99 (100 µmol/kg) once daily for 4 days (n = 3–5/group). Gut microbiome was characterized using 16S rRNA sequencing of the large intestinal content in CV mice. Both BDE-47 and BDE-99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. Both PBDE congeners increased Akkermansia muciniphila and Erysipelotrichaceae Allobaculum spp., which have been reported to have anti-inflammatory and antiobesity functions. Targeted metabolomics of 56 BAs was conducted in serum, liver, and small and large intestinal content of CV and GF mice. BDE-99 increased many unconjugated BAs in multiple biocompartments in a gut microbiota-dependent manner. This correlated with an increase in microbial 7α-dehydroxylation enzymes for secondary BA synthesis and increased expression of host intestinal transporters for BA absorption. Targeted proteomics showed that PBDEs downregulated host BA-synthesizing enzymes and transporters in livers of CV but not GF mice. In conclusion, there is a novel interaction between PBDEs and the endogenous BA-signaling through modification of the “gut-liver axis”.

AB - Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothesis that PBDEs cause dysbiosis and aberrant regulation of BA homeostasis. Nine-week-old male C57BL/6 conventional (CV) and germ-free (GF) mice were orally gavaged with corn oil (10 mg/kg), BDE-47 (100 µmol/kg), or BDE-99 (100 µmol/kg) once daily for 4 days (n = 3–5/group). Gut microbiome was characterized using 16S rRNA sequencing of the large intestinal content in CV mice. Both BDE-47 and BDE-99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. Both PBDE congeners increased Akkermansia muciniphila and Erysipelotrichaceae Allobaculum spp., which have been reported to have anti-inflammatory and antiobesity functions. Targeted metabolomics of 56 BAs was conducted in serum, liver, and small and large intestinal content of CV and GF mice. BDE-99 increased many unconjugated BAs in multiple biocompartments in a gut microbiota-dependent manner. This correlated with an increase in microbial 7α-dehydroxylation enzymes for secondary BA synthesis and increased expression of host intestinal transporters for BA absorption. Targeted proteomics showed that PBDEs downregulated host BA-synthesizing enzymes and transporters in livers of CV but not GF mice. In conclusion, there is a novel interaction between PBDEs and the endogenous BA-signaling through modification of the “gut-liver axis”.

UR - http://www.scopus.com/inward/record.url?scp=85050797865&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050797865&partnerID=8YFLogxK

U2 - 10.1124/dmd.118.081547

DO - 10.1124/dmd.118.081547

M3 - Article

VL - 46

SP - 1226

EP - 1240

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 8

ER -