Gut Microbiota Modulates Interactions Between Polychlorinated Biphenyls and Bile Acid Homeostasis

Sunny Lihua Cheng; Xueshu Li; Hans-Joachim Lehmler; Brian Phillips; Danny Shen; Julia Yue Cui

doi:10.1093/toxsci/kfy208

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Gut Microbiota Modulates Interactions Between Polychlorinated Biphenyls and Bile Acid Homeostasis

Journal article

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Peer reviewed

Gut Microbiota Modulates Interactions Between Polychlorinated Biphenyls and Bile Acid Homeostasis

Sunny Lihua Cheng, Xueshu Li, Hans-Joachim Lehmler, Brian Phillips, Danny Shen and Julia Yue Cui

Toxicological sciences, Vol.166(2), pp.269-287

12/2018

DOI: 10.1093/toxsci/kfy208

PMCID: PMC6260149

PMID: 30496569

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Abstract

The gut microbiome is increasingly recognized as a second genome that contributes to the health and diseases of the host. A major function of the gut microbiota is to convert primary bile acids (BAs) produced from cholesterol in the liver into secondary BAs that activate distinct host receptors to modulate xenobiotic metabolism and energy homeostasis. The goal of this study was to investigate to what extent oral exposure to an environmentally relevant polychlorinated biphenyl (PCBs mixture), namely the Fox River mixture, impacts gut microbiome and BA homeostasis. Ninety-day-old adult female conventional (CV) and germ-free (GF) C57BL/6 mice were orally exposed to corn oil (vehicle), or the Fox River mixture at 6 or 30 mg/kg once daily for 3 consecutive days. The PCB low dose profoundly increased BA metabolism related bacteria Akkermansia ( A. ) muciniphila , Clostridium ( C. ) scindens , and Enterococcus in the large intestinal pellet (LIP) of CV mice (16S rRNA sequencing/qPCR). This correlated with a PCB low dose-mediated increase in multiple BAs in serum and small intestinal content (SIP) in a gut microbiota-dependent manner (UPLC-MS/MS). Conversely, at PCB high dose, BA levels remained stable in CV mice correlated with an increase in hepatic efflux transporters and ileal Fgf15. Interestingly, lack of gut microbiota potentiated the PCB-mediated increase in taurine conjugated α and β muricholic acids in liver, SIP, and LIP. Pearson’s correlation identified positive correlations between 5 taxa and most secondary BAs. In conclusion, PCBs dose-dependently altered BA homeostasis through a joint effort between host gut-liver axis and intestinal bacteria.

GUT MICROBIOME, PCBs, AND BILE ACIDS

PCBs

bile acids

liver

gut microbiota

Synthesis Core

Details

Title: Subtitle: Gut Microbiota Modulates Interactions Between Polychlorinated Biphenyls and Bile Acid Homeostasis
Creators: Sunny Lihua Cheng - Department of Pharmaceutical Sciences, University of Washington, Seattle, Washington, 98105
Xueshu Li - Department of Pharmaceutical Sciences, University of Washington, Seattle, Washington, 98105
Hans-Joachim Lehmler - Department of Pharmaceutical Sciences, University of Washington, Seattle, Washington, 98105
Brian Phillips - Department of Pharmaceutical Sciences, University of Washington, Seattle, Washington, 98105
Danny Shen - Department of Pharmaceutical Sciences, University of Washington, Seattle, Washington, 98105
Julia Yue Cui - Department of Pharmaceutical Sciences, University of Washington, Seattle, Washington, 98105
Resource Type: Journal article
Publication Details: Toxicological sciences, Vol.166(2), pp.269-287
DOI: 10.1093/toxsci/kfy208
PMID: 30496569
PMCID: PMC6260149
NLM abbreviation: Toxicol Sci
ISSN: 1096-6080
eISSN: 1096-0929
Publisher: Oxford University Press
Grant note: P30 ES005605; P42 ES013661; R01 GM111381 / ; ; ; P30 ES0007033 / ; ;
Language: English
Date published: 12/2018
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Biology; Iowa Superfund Research Program
Record Identifier: 9984001080202771

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