Published online Jun 14, 2023. doi: 10.3748/wjg.v29.i22.3534
Peer-review started: February 26, 2023
First decision: March 10, 2023
Revised: March 15, 2023
Accepted: May 4, 2023
Article in press: May 4, 2023
Published online: June 14, 2023
Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC).
Metabolites in enterohepatic circulation play an important role in cross-talk between liver and gut. The metabolites in the blood or the feces may have homogeneity but may also have specific characteristics related to their respective environments. The correlation between intestinal and plasma metabolites in patients with ALC, which might be helpful for the diagnosis and treatment of ALC, has not yet been elucidated.
To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.
This was a case-controlled observation study. We prospectively enrolled two groups of subjects: individuals with ALC and healthy controls (HCs). We recruited age-matched healthy males as controls through recruitment advertisements. According to the inclusion and exclusion criteria, 27 patients with ALC and 24 HCs were selected. The plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites. Also, the association of metabolites with clinical features was analyzed.
More than 8000 plasma and more than 10000 fecal metabolites of patients with ALC were detected. Among them, More than 300 metabolites were found both in the plasma and feces. Enrichment analysis showed that these common metabolites are enriched in bile and amino acid metabolic pathways. Moreover, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. These results was consistent with previous studies and have indeed confirmed the disorder of bile acid and amino acid metabolism in patients with ALC. Besides, GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. AP/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score was established, which may be used as a biomarker of the severity of ALC.
Bile acid and amino acid metabolism play a very important role in the progression of ALC. The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces was related to the severity of ALC. The P/S BA ratio of plasma primary bile acids (GCA and TCA) to fecal secondary bile acid (DCA), was relevant to TBil, PT, and MDF score.
Integrating intestinal microbiomics and metabolomics analysis is essential to decipher the molecular mechanisms underlying ALC. Since LC-MS analysis used in this study has limitations, further comparisons with other detection methods and complementary studies are required.