التفاصيل البيبلوغرافية
| العنوان: |
The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice. |
| المؤلفون: |
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 |
| المصدر: |
Microbiome; 4/20/2021, Vol. 9 Issue 1, p1-16, 16p |
| مصطلحات موضوعية: |
GUT microbiome, PREGNANE X receptor, XENOBIOTICS, DRUG interactions, ANIMAL models in research |
| مستخلص: |
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. 6jaknk__LWi2dgNs2otrXU Video abstract [ABSTRACT FROM AUTHOR] |
|
Copyright of Microbiome is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder