Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/152006
Title: The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice
Authors: Barretto, Sharon Ann
Lasserre, Frederic
Huillet, Marine
Régnier, Marion
Polizzi, Arnaud
Lippi, Yannick
Fougerat, Anne
Person, Elodie
Bruel, Sandrine
Bétoulières, Colette
Naylies, Claire
Lukowicz, Céline
Smati, Sarra
Guzylack, Laurence
Olier, Maïwenn
Théodorou, Vassilia
Mselli-Lakhal, Laila
Zalko, Daniel
Wahli, Walter
Loiseau, Nicolas
Gamet-Payrastre, Laurence
Guillou, Hervé
Ellero-Simatos, Sandrine
Keywords: Science::Biological sciences
Issue Date: 2021
Source: 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., ...Ellero-Simatos, S. (2021). The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice. Microbiome, 9(1), 93-. https://dx.doi.org/10.1186/s40168-021-01050-9
Journal: Microbiome 
Abstract: Background: 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. Results: 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+/+ vs Pxr-/- 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+/+ but not Pxr-/- male mice. Conclusions: 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.
URI: https://hdl.handle.net/10356/152006
ISSN: 2049-2618
DOI: 10.1186/s40168-021-01050-9
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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