New research has identified a biological pathway linking psychological stress to faster progression of hepatocellular carcinoma (HCC), the most common form of liver cancer. The study shows how stress disrupts the gut microbiome, leading to changes in bacterial metabolites that alter immune signaling within the tumor microenvironment.
Key findings include a significant reduction in the beneficial bacterium Phocaeicola vulgatus under stress conditions. Restoring levels of this bacterium, or administering its key metabolite indole-3-propionic acid, significantly slowed tumor growth in experimental models.
The metabolite was shown to reduce expression of JAM2, a protein involved in endothelial signaling, thereby disrupting interactions between endothelial cells and macrophages that support tumor growth and immune evasion.
Researchers describe a multi-layered stress-gut-tumor axis, suggesting that targeting this pathway through microbiome-based interventions could complement existing liver cancer treatments, particularly for patients experiencing chronic stress.