# Gut microbiota–immunity cascade in hepatocellular carcinoma: mechanisms and therapeutic opportunities

## TL;DR

This review explores how gut bacteria influence liver cancer development and treatment, highlighting their potential as biomarkers and therapeutic targets.

## Contribution

The paper provides a comprehensive synthesis of gut microbiota's role in HCC immunology and therapeutic strategies.

## Key findings

- Gut dysbiosis is a characteristic feature in hepatocellular carcinoma.
- Microbial metabolites modulate the tumor immune microenvironment with dual roles in immunity and suppression.
- Specific gut microbiota signatures correlate with immunotherapy efficacy in HCC.

## Abstract

Hepatocellular carcinoma (HCC) constitutes a major global health burden, with limited responsiveness to current immunotherapeutic regimens. Accumulating evidence underscores the gut microbiota as a crucial regulator of the gut–liver axis, modulating tumor initiation, immune evasion, and the outcomes of immunotherapeutic interventions—and notably, it concurrently exhibits both potential diagnostic biomarker value and actionable therapeutic target properties. In the present review, we synthesize the characteristic features of gut dysbiosis in HCC, delineate the mechanisms by which microbial metabolites—including short-chain fatty acids (SCFAs), bile acids, and indoles—modulate the tumor immune microenvironment (TME), and elaborate on their dual roles in promoting anti-tumor immunity while concomitantly mediating immune suppression. We further examine the clinical correlations between specific microbial taxa and the efficacy of immune checkpoint inhibitors (ICIs)—findings that support the utility of gut microbiota signatures as predictive or diagnostic biomarkers—and explore emerging microbiota-targeted strategies, such as fecal microbiota transplantation (FMT), probiotic supplementation, phage therapy, and dietary modulation, which validate the gut microbiota as a viable therapeutic target.