Hepatocellular carcinoma (HCC) is the terminal phase of multiple chronic
liver diseases, and evidence supports chronic uncontrollable
inflammation being one of the potential mechanisms leading to HCC formation. The dysregulation of
bile acid homeostasis in the enterohepatic circulation has become a hot research issue concerning revealing the pathogenesis of the inflammatory-cancerous transformation process. We reproduced the development of HCC through an
N-nitrosodiethylamine (DEN)-induced rat model in 20 weeks. We achieved the monitoring of the
bile acid profile in the plasma, liver, and intestine during the evolution of "
hepatitis-
cirrhosis-HCC" by using an ultra-performance liquid chromatography-tandem mass spectrometer for absolute quantification of
bile acids. We observed differences in the level of primary and secondary
bile acids both in plasma, liver, and intestine when compared to controls, particularly a sustained reduction of intestine
taurine-conjugated
bile acid level. Moreover, we identified
chenodeoxycholic acid,
lithocholic acid,
ursodeoxycholic acid, and
glycolithocholic acid in plasma as
biomarkers for early diagnosis of HCC. We also identified
bile acid-CoA:amino acid N-acyltransferase (BAAT) by gene set enrichment analysis, which dominates the final step in the synthesis of conjugated
bile acids associated with the inflammatory-
cancer transformation process. In conclusion, our study provided comprehensive
bile acid metabolic fingerprinting in the liver-gut axis during the
inflammation-
cancer transformation process, laying the foundation for providing a new perspective for the diagnosis, prevention, and treatment of HCC.