Stress accelerates hepatocellular carcinoma progression via a gut microbial-metabolite axis

In this study, we integrated clinical and preclinical models to investigate how stress-associated gut microbiota remodeling contributes to hepatocellular carcinoma progression. Stress profoundly altered the gut microbiota, with Phocaeicola vulgatus significantly reduced.

Restoration of Phocaeicola vulgatus or administration of its tryptophan-derived metabolite indole-3-propionic acid attenuated hepatocellular carcinoma progression in vivo. Single-cell RNA sequencing was performed to characterize changes in the hepatocellular carcinoma tumor microenvironment. Indole-3-propionic acid treatment reduced endothelial JAM2 expression and was associated with reduced JAM2-F11R-mediated endothelial-macrophage crosstalk.