Researchers Link Gut Microbiome Modulation to Better Liver Cancer Immunotherapy Outcomes

A growing body of research suggests the gut microbiome may play a key role in determining how well people with advanced liver cancer respond to immunotherapy. A new review published in Cancer Biology & Medicine highlights how microbes in the gut and liver influence the tumor’s immune environment, potentially affecting treatment success and resistance in hepatocellular carcinoma (HCC), the most common form of liver cancer. 

Although immune checkpoint inhibitors have improved outcomes for some patients, only a small proportion achieve long-lasting responses. Researchers from The Chinese University of Hong Kong reviewed recent evidence showing that the gut-liver axis—a communication network linking the intestine and liver—plays an important role in regulating anti-tumor immunity.

Healthy gut bacteria produce beneficial compounds such as short-chain fatty acids that help maintain immune balance. In contrast, microbial imbalance in HCC promotes the growth of harmful bacteria that generate inflammatory metabolites, including deoxycholic acid and quinolinic acid, which may encourage tumor growth and suppress immune defenses.

Researchers further highlighted microbial signatures linked to poor immunotherapy response. Some bacteria appear to disrupt tryptophan metabolism, reducing beneficial metabolites and weakening the activity of CD8+ T cells, which are essential for destroying cancer cells.

The authors suggest that the gut microbiome is more than a biomarker—it may actively shape treatment outcomes. This opens the possibility of improving immunotherapy through microbiome-targeted strategies such as probiotics, high-fiber diets, or fecal microbiota transplantation (FMT).

Several clinical trials are already investigating these approaches, including studies combining FMT with immunotherapy in patients who previously failed treatment. While further research is needed, scientists believe modifying the gut microbiome could eventually help identify likely responders, overcome treatment resistance, reduce immune-related side effects, and improve outcomes for people with advanced liver cancer.

REFERENCE: Wu, M., et al. (2026). How the gut microbiome affects the immunotherapy response in hepatocellular carcinoma. Cancer Biology & Medicine. DOI: 10.20892/j.issn.2095-3941.2025.0761. https://www.cancerbiomed.org/content/early/2026/04/10/j.issn.2095-3941.2025.0761