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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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