Published online Apr 21, 2025. doi: 10.3748/wjg.v31.i15.104996
Revised: February 18, 2025
Accepted: March 24, 2025
Published online: April 21, 2025
Processing time: 100 Days and 5 Hours
Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is a key contributor to cancer-related deaths globally. However, HCC diagnosis solely based on blood biochemical markers lacks both sensitivity and specificity.
To investigate alterations of the fecal metabolome and intestinal bacteria and reveal the correlations among differential metabolites, distinct bacteria, and serum indicators.
To uncover potentially effective therapeutic targets for HCC, we utilized non-targeted liquid chromatography-mass spectrometry and high-throughput DNA sequencing targeting the 16S rRNA gene. This comprehensive approach allowed us to investigate the metabolome and microbial community structure of feces samples obtained from patients with HCC. Furthermore, we con
In comparison to healthy controls, a notable overlap of 161 differential metabolites and 3 enriched Kyoto Encyclopedia of Genes and Genomes pathways was observed in the HCC12 (comprising patients with stage I and II HCC) and HCC34 groups (comprising patients with stage III and IV HCC). Lachnospira, Streptococcus, and Veillonella had significant differences in abundance in patients with HCC. Notably, Streptococcus and Veillonella exhibited significant correlations with serum indicators such as alpha-fetoprotein (AFP). Meanwhile, several differential metabolites [e.g., 4-keto-2-undecylpyrroline, dihydrojasmonic acid, 1,8-heptadecadiene-4,6-diyne-3,10-diol, 9(S)-HOTrE] also exhibited significant correlations with serum indicators such as γ-glutamyl transferase, total bilirubin, AFP, aspartate aminotransferase, and albumin. Additionally, these two genera also had significant associations with differential metabolites such as 1,2-Dipentadecanoyl-rac-glycerol (15:0/20:0/0:0), arachidoyl ethanolamide, and 4-keto-2-undecylpyrroline.
Our results suggest that the metabolome of fecal samples and the composition of intestinal bacteria hold promise as potential biomarkers for HCC diagnosis.
Core Tip: This study investigated the alterations in the fecal metabolome and intestinal bacteria, and elucidated the correlations among differential metabolites, distinct bacterial taxa, and serum indicators. By employing non-targeted liquid chromatography-mass spectrometry and high-throughput DNA sequencing technologies, the researchers discovered that three Kyoto Encyclopedia of Genes and Genomes pathways, namely retinol metabolism, steroid hormone biosynthesis, and ascorbate and aldarate metabolism, were significantly enriched by differential metabolites, along with three representative bacterial genera: Streptococcus, Veillonella, and Lachnospira. Notably, Streptococcus and Veillonella exhibited evident correlations with serum indicators and differential metabolites. The findings suggest that the fecal metabolome and the composition of intestinal bacteria hold considerable potential as biomarkers for the diagnosis of hepatocellular carcinoma.