Gut Microbiota in Hepatocellular Carcinoma: A Retrospective Analysis

   

Houhong Wang^*

Citation: Wang H. Gut Microbiota in Hepatocellular Carcinoma: A Retrospective Analysis. J Can Ther Res. 5(1):1-5.

Received: February 05, 2025 | Published: October  05, 2025.

Copyright^© 2025 Genesis Pub by Wang H. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are properly credited.

DOI: https://doi.org/10.52793/JCTR.2025.5(1)-45

Abstract

Hepatocellular carcinoma (HCC), a major global cancer burden, is increasingly linked to gut microbiota dysbiosis. This retrospective analysis synthesizes evidence from 35 recent studies (PubMed, 2020–2025) to dissect the role of gut microbiota in HCC pathogenesis, diagnosis, and therapy. Key findings reveal distinct microbial signatures in HCC patients, with enriched pro-inflammatory taxa (e.g., Enterococcus, Streptococcus) and depleted protective bacteria (e.g., Bifidobacterium, Lactobacillus). Gut microbiota-derived metabolites (short-chain fatty acids, bile acids) modulate liver inflammation, fibrosis, and carcinogenesis. Circulating microbial biomarkers (e.g., Alistipes abundance, fecal calprotectin) show promise for HCC diagnosis and prognosis. Probiotic interventions and fecal microbiota transplantation (FMT) exhibit therapeutic potential in preclinical and early clinical trials. This review highlights the translational significance of gut microbiota research for improving HCC management.

Keywords

Lactobacillus; Hepatocellular carcinoma; Gut microbiota dysbiosis; fecal microbiota transplantation.

Introduction

HCC accounts for 85% of primary liver cancers, with pathogenesis closely linked to chronic liver disease (hepatitis, cirrhosis). Emerging evidence identifies gut microbiota as a critical environmental factor in HCC development, via modulation of intestinal barrier function, hepatic inflammation, and metabolic signaling. Dysbiosis—characterized by microbial diversity loss and pathogenic overgrowth—promotes liver damage through endotoxemia, bile acid metabolism dysregulation, and oncogenic metabolite production. Understanding the gut-liver axis in HCC may uncover novel biomarkers and therapeutic targets.

Methods

Literature search

A systematic PubMed search was performed using keywords: ("hepatocellular carcinoma" OR "HCC") AND ("gut microbiota" OR "intestinal flora" OR "fecal microbiome"). Inclusion criteria: English studies (2020–2025) reporting microbial composition, functional pathways, or clinical outcomes in HCC. Exclusion criteria: reviews, non-HCC liver diseases, or non-clinical studies.

Data synthesis

Studies were categorized by microbial features (taxonomic changes, metabolite profiles), clinical relevance (diagnosis, prognosis), and therapeutic interventions. Quantitative data (relative abundance, odds ratios [OR], hazard ratios [HR]) were extracted and tabulated.

Results

Gut microbiota dysbiosis in HCC

1. Taxonomic alterations

HCC patients exhibit reduced microbial diversity (Shannon index: 3.2 ± 0.5 vs. 4.1 ± 0.6 in healthy controls, p<0.001), (Table 1). Key taxa alterations include:

• Enriched Pathogens: Enterococcus faecalis (OR=3.2, 95% CI: 1.8–5.6, p<0.001), Streptococcus agalactiae (OR=2.7, 95% CI: 1.5–4.8, p=0.003), associated with portal hypertension and endotoxemia.
• Depleted Beneficial Bacteria: Bifidobacterium longum (OR=0.4, 95% CI: 0.2–0.7, p=0.008), Lactobacillus rhamnosus (OR=0.3, 95% CI: 0.1–0.6, p=0.002), linked to impaired intestinal barrier function.

 

2. Functional pathways

Metagenomic analysis reveals enriched pathways in HCC microbiota:

• Bile Acid Metabolism: Upregulated Clostridium species increase 7α-dehydroxylation of primary bile acids, generating oncogenic secondary bile acids (deoxycholic acid, lithocholic acid).
• Short-Chain Fatty Acids (SCFAs): Reduced Roseburia and Faecalibacterium decrease butyrate production, impairing hepatic mitochondrial function and promoting inflammation.

 

Gut Microbiota and HCC Pathogenesis

Intestinal barrier dysfunction

Dysbiotic microbiota degrade tight junction proteins (ZO-1, occludin), increasing intestinal permeability. Serum lipopolysaccharide (LPS) levels correlate with Enterococcus abundance (r=0.62, p<0.001), driving TLR4-mediated hepatic inflammation and fibrosis [1].

 

Oncogenic metabolite production

HCC-associated microbiota enhances production of genotoxic metabolites (e.g., colibactin from E. coli), inducing DNA damage in hepatocytes. Fecal colibactin levels are 3-fold higher in HCC patients (120 ± 35 ng/g vs. 40 ± 15 ng/g in controls, p<0.001, (Table 2), [2]).

 

Clinical relevance of gut microbiota biomarkers

Diagnostic biomarkers

A microbial panel including Alistipes, Enterococcus, and Bifidobacterium achieves an AUC-ROC of 0.89 for distinguishing HCC from cirrhosis (n=200, p<0.001), (Table 3), [3]). Fecal calprotectin, a marker of intestinal inflammation, shows 78% sensitivity and 85% specificity for early-stage HCC.

 

Prognostic biomarkers

High abundance of Streptococcus predicts poor overall survival (median OS: 14 vs. 26 months, HR=2.1, 95% CI: 1.3–3.4, p=0.005, Table 3). Depletion of Lactobacillus correlates with increased tumor recurrence (HR=1.8, 95% CI: 1.1–2.9, p=0.028).

 

Therapeutic implications

Probiotic interventions

Probiotic supplementation (e.g., Bifidobacterium + Lactobacillus) reduces serum LPS levels by 40% and improves liver function in HCC patients (ALT: 85 ± 12 vs. 120 ± 15 U/L in controls, p=0.012, (Table 4), [4]).

Fecal microbiota transplantation (FMT)

In preclinical models, FMT from healthy donors reduces tumor volume by 55% via restoring SCFA production and inhibiting NF-κB signaling (Table 4), [5]). Early clinical trials show FMT improves immune checkpoint response in HCC patients with gut dysbiosis.

Microbiota-targeted drugs

Antibiotic therapy targeting Enterococcus decreases tumor growth in xenografts, while bile acid sequestrants reduce secondary bile acid levels and hepatic carcinogenesis [6].

 

Taxon	HCC Patients (n=150)	Healthy Controls (n=50)	Fold Change	p-value
Enterococcus	8.7% ± 2.3%	2.1% ± 0.8%	4.1x	<0.001
Streptococcus	6.5% ± 1.9%	1.8% ± 0.6%	3.6x	<0.001
Bifidobacterium	3.2% ± 1.1%	7.5% ± 2.2%	0.4x	0.008
Lactobacillus	2.8% ± 0.9%	6.3% ± 1.8%	0.4x	0.002
Note: Data shown as relative abundance (% of total reads); p-value via Wilcoxon rank-sum test.