The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice.
Fatty acid metabolism
Gut microbiota
Liver
NR1I2
Pregnane X receptor
Transcriptomics
Xenobiotic metabolism
Journal
Microbiome
ISSN: 2049-2618
Titre abrégé: Microbiome
Pays: England
ID NLM: 101615147
Informations de publication
Date de publication:
20 04 2021
20 04 2021
Historique:
received:
02
02
2021
accepted:
16
03
2021
entrez:
21
4
2021
pubmed:
22
4
2021
medline:
7
5
2021
Statut:
epublish
Résumé
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 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.
Sections du résumé
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
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. Video abstract.
Identifiants
pubmed: 33879258
doi: 10.1186/s40168-021-01050-9
pii: 10.1186/s40168-021-01050-9
pmc: PMC8059225
doi:
Substances chimiques
Lipids
0
Nr1i2 protein, mouse
0
Pregnane X Receptor
0
Xenobiotics
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
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