Etiology-associated differences in the gut microbiome and metabolome in hepatocellular carcinoma: an exploratory study of alcohol-related and HBV-related cases
- 1Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University , , ,
- 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University , ,
- 3Guangxi Medical University , ,
Abstract
Hepatocellular carcinoma (HCC) arises in heterogeneous etiological contexts, but direct cross-omics comparisons between HCC subgroups defined by different etiologies remain limited. In this exploratory study, we combined fecal 16S rRNA gene sequencing and untargeted serum metabolomics with exploratory cross-omics analyses to compare gut microbial composition, serum metabolic profiles, and microbiome–metabolite association patterns between hepatitis B virus-related HCC (HBV-HCC) and alcohol-related HCC (ALD-HCC). Forty patients who underwent primary tumor resection were included, comprising 26 with HBV-HCC and 14 with ALD-HCC. Alpha diversity indices did not differ significantly between groups, whereas within-group Bray–Curtis dissimilarity was greater in ALD-HCC and genus-level beta-diversity ordination showed only modest separation between the two groups. LEfSe-based screening suggested the enrichment of candidate taxa, including Faecalibacterium , Roseburia , Lachnospira , Turicibacter , and Butyribacter in HBV-HCC, whereas Allisonella and Coprobacillus were enriched in ALD-HCC. Untargeted metabolomics showed group separation in supervised models and identified exploratory candidate metabolic features mainly involving glycerophospholipid metabolism, primary bile acid biosynthesis, aminoacyl-tRNA biosynthesis, and central carbon metabolism in cancer; however, these metabolite-level findings did not remain significant after multiple-testing correction. Procrustes and O2PLS analyses indicated limited global concordance between the microbiome and metabolome, although exploratory associations were observed between several phosphatidylcholine-related features and microbial taxa. Overall, HBV-HCC and ALD-HCC may be associated with different gut microbial and serum metabolic patterns, and these findings should be considered exploratory and hypothesis-generating.
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BibTeX
@article{wei2026etiologyassociated,
title = {{Etiology-associated differences in the gut microbiome and metabolome in hepatocellular carcinoma: an exploratory study of alcohol-related and HBV-related cases}},
author = {Yongguang Wei and Kejian Yang and Qinchen Lu and Xin Zhou and Huasheng Huang and Meiliang Liu and Lijun Wang and Liming Shang and Tao Peng and Xiaoyun Zeng},
journal = {Frontiers in microbiology},
year = {2026},
month = sep,
doi = {10.3389/fmicb.2026.1927595},
url = {https://europepmc.org/article/PMC/PMC13671147},
note = {CC BY},
}
RIS
TY - JOUR
TI - Etiology-associated differences in the gut microbiome and metabolome in hepatocellular carcinoma: an exploratory study of alcohol-related and HBV-related cases
AU - Yongguang Wei
AU - Kejian Yang
AU - Qinchen Lu
AU - Xin Zhou
AU - Huasheng Huang
AU - Meiliang Liu
AU - Lijun Wang
AU - Liming Shang
AU - Tao Peng
AU - Xiaoyun Zeng
PY - 2026
DA - 2026/09/30
JO - Frontiers in microbiology
DO - 10.3389/fmicb.2026.1927595
UR - https://europepmc.org/article/PMC/PMC13671147
AB - Hepatocellular carcinoma (HCC) arises in heterogeneous etiological contexts, but direct cross-omics comparisons between HCC subgroups defined by different etiologies remain limited. In this exploratory study, we combined fecal 16S rRNA gene sequencing and untargeted serum metabolomics with exploratory cross-omics analyses to compare gut microbial composition, serum metabolic profiles, and microbiome–metabolite association patterns between hepatitis B virus-related HCC (HBV-HCC) and alcohol-related HCC (ALD-HCC). Forty patients who underwent primary tumor resection were included, comprising 26 with HBV-HCC and 14 with ALD-HCC. Alpha diversity indices did not differ significantly between groups, whereas within-group Bray–Curtis dissimilarity was greater in ALD-HCC and genus-level beta-diversity ordination showed only modest separation between the two groups. LEfSe-based screening suggested the enrichment of candidate taxa, including Faecalibacterium , Roseburia , Lachnospira , Turicibacter , and Butyribacter in HBV-HCC, whereas Allisonella and Coprobacillus were enriched in ALD-HCC. Untargeted metabolomics showed group separation in supervised models and identified exploratory candidate metabolic features mainly involving glycerophospholipid metabolism, primary bile acid biosynthesis, aminoacyl-tRNA biosynthesis, and central carbon metabolism in cancer; however, these metabolite-level findings did not remain significant after multiple-testing correction. Procrustes and O2PLS analyses indicated limited global concordance between the microbiome and metabolome, although exploratory associations were observed between several phosphatidylcholine-related features and microbial taxa. Overall, HBV-HCC and ALD-HCC may be associated with different gut microbial and serum metabolic patterns, and these findings should be considered exploratory and hypothesis-generating.
SN - 1664-302X
ER -