Gut Microbiota Affects Mouse Pregnane X Receptor Agonist Pregnenolone 16α-Carbonitrile-Induced Hepatomegaly by Regulating Pregnane X Receptor and Yes-Associated Protein Activation
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View abstract on PubMed
Summary
This summary is machine-generated.Gut microbiota influences liver enlargement caused by pregnane X receptor (PXR) activation. Antibiotics reduce this effect, while microbiota transplants restore it, highlighting microbial regulation of PXR and YAP pathways.
Area Of Science
- Hepatology and Gastroenterology
- Molecular Biology and Pharmacology
Background
- Pregnane X receptor (PXR) regulates liver homeostasis, and its activation promotes liver enlargement via yes-associated protein (YAP).
- The gut microbiota's role in PXR-mediated hepatomegaly and its underlying mechanisms are not fully understood.
Purpose Of The Study
- To investigate the contribution of gut microbiota to pregnenolone 16α-carbonitrile (PCN)-induced liver enlargement.
- To elucidate the mechanisms by which gut microbiota influences PXR and YAP activation in hepatomegaly.
Main Methods
- C57BL/6 mice were treated with the PXR agonist PCN.
- Gut microbiota was depleted using antibiotics (ABX) and restored via fecal microbiota transplantation (FMT).
- Microbiota composition (16S rRNA sequencing) and expression of PXR, YAP, and downstream targets were analyzed.
Main Results
- PCN treatment altered gut microbiota composition and abundance.
- ABX-induced microbiota depletion significantly attenuated PCN-induced hepatomegaly.
- FMT from PCN-treated mice induced liver enlargement in recipient mice, impairing PXR and YAP activation.
Conclusions
- Gut microbiota plays a crucial role in PCN-induced hepatomegaly.
- Microbiota modulates PXR and YAP activation, contributing to liver enlargement.
- Findings offer novel insights into gut microbiota's involvement in PXR-mediated liver pathophysiology.
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