To investigate the systemic effects of Nurr1 haplo-insufficiency on liver-gut inter-organ communication and to characterize the resulting pathological conditions.
Approach:
Key Findings:
Nurr1 haplo-insufficiency leads to hepatocellular necrosis and activation of inflammatory and pro-fibrotic genes.
Dysregulation of the intestinal barrier and severe small-intestinal dysbiosis were observed.
A transcriptional signature of liver-gut disorder achieved up to 0.950 accuracy in classifying genotypes.
AI algorithms achieved 99.50% accuracy in classifying hepatic fibrosis and 99.20% in liver inflammation.
Interpretation:
Nurr1 plays a crucial regulatory role in maintaining liver-gut homeostasis, with its deficiency leading to significant pathological changes.
Limitations:
The study primarily focuses on a murine model, which may not fully replicate human conditions.
The implications of Nurr1 deficiency in other organ systems remain to be explored.
Conclusion:
This study provides a comprehensive multi-omics phenotype of Nurr1 deficiency and establishes a framework for AI-driven histopathological analysis.
