The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice.

Details

Serval ID
serval:BIB_BC662F439698
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice.
Journal
Microbiome
Author(s)
Barretto S.A., Lasserre F., Huillet M., Régnier M., Polizzi A., Lippi Y., Fougerat A., Person E., Bruel S., Bétoulières C., Naylies C., Lukowicz C., Smati S., Guzylack L., Olier M., Théodorou V., Mselli-Lakhal L., Zalko D., Wahli W., Loiseau N., Gamet-Payrastre L., Guillou H., Ellero-Simatos S.
ISSN
2049-2618 (Electronic)
ISSN-L
2049-2618
Publication state
Published
Issued date
20/04/2021
Peer-reviewed
Oui
Volume
9
Number
1
Pages
93
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
Publication Status: epublish
Abstract
The gut microbiota-intestine-liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined.
By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion using antibiotics in Pxr <sup>+/+</sup> vs Pxr <sup>-/-</sup> C57BL/6J littermate mice followed by hepatic transcriptomics revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis suggested that microbiota-PXR interaction controlled fatty acid and xenobiotic metabolism. We confirmed that antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in the liver from Pxr <sup>+/+</sup> but not Pxr <sup>-/-</sup> male mice.
These findings identify PXR as a hepatic effector of microbiota-derived signals that regulate the host's sexually dimorphic lipid and xenobiotic metabolisms in the liver. Thus, our results reveal a potential new mechanism for unexpected drug-drug or food-drug interactions. Video abstract.
Keywords
Animals, Female, Gastrointestinal Microbiome/genetics, Lipids, Liver, Male, Mice, Mice, Inbred C57BL, Pregnane X Receptor/genetics, Xenobiotics, Fatty acid metabolism, Gut microbiota, NR1I2, Pregnane X receptor, Transcriptomics, Xenobiotic metabolism
Pubmed
Web of science
Open Access
Yes
Create date
26/04/2021 9:37
Last modification date
07/06/2021 6:36
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