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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma
Jing Feng, Jun-Ping Wang, Jian-Ran Hu, Ping Li, Pin Lv, Hu-Cheng He, Xiao-Wei Cheng, Zheng Cao, Jia-Jing Han, Qiang Wang, Qian Su, Li-Xin Liu
Jing Feng, Li-Xin Liu, Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Jing Feng, Qiang Wang, Qian Su, Department of Infectious Diseases and Hepatology, Shanxi Provincial People’s Hospital, Affiliated to Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Jun-Ping Wang, Pin Lv, Hu-Cheng He, Zheng Cao, Jia-Jing Han, Department of Gastroenterology, Shanxi Provincial People’s Hospital, Affiliated to Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Jian-Ran Hu, Ping Li, Department of Biological Science and Technology, Jinzhong University, Jinzhong 030619, Shanxi Province, China
Xiao-Wei Cheng, Department of Interventional Therapy, Shanxi Provincial People’s Hospital, Affiliated to Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Author contributions: Feng J conceived and designed the experiments, performed the experiments, and analyzed the data; Wang JP performed the experiments, and analyzed the data; Hu JR and Li P analyzed the data and prepared figures and/or tables; Lv P, He HC, Cheng XW, Cao Z, Han JJ, Wang Q, and Su Q performed the experiments; Liu LX conceived and designed the experiments and authored or reviewed drafts of the article; All authors read and approved the final manuscript.
Supported by the Department of Science and Technology of Shanxi Province, No. 20210302124369; the Health Commission of Shanxi Province, No. 2021116; and Shanxi Administration of Traditional Chinese Medicine, No. 2024ZYY2C054.
Institutional review board statement: The study protocol was approved by the medical ethics committee of Shanxi Provincial People’s Hospital (No. 2021-45).
Institutional animal care and use committee statement: This study does not involve any animal-related experiments.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Li-Xin Liu, Department of Gastroenterology, The First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Yingze District, Taiyuan 030001, Shanxi Province, China.
lixinliu6@hotmail.com
Received: January 9, 2025
Revised: February 18, 2025
Accepted: March 24, 2025
Published online: April 21, 2025
Processing time: 100 Days and 5 Hours
BACKGROUND
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.
AIM
To investigate alterations of the fecal metabolome and intestinal bacteria and reveal the correlations among differential metabolites, distinct bacteria, and serum indicators.
METHODS
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 conducted an analysis to assess the interplay between the fecal metabolome and intestinal bacterial population.
RESULTS
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.
CONCLUSION
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.
