Indole-3-propionic acid treatment reduced endothelial JAM2 expression and was associated with reduced JAM2-F11R-mediated endothelial-macrophage crosstalk in hepatocellular carcinoma, which may contribute to suppression of tumor progression.<h4>Conclusions</h4>These findings support a role for the stress-gut microbiota-metabolite-tumor microenvironment axis in hepatocellular carcinoma progression and suggest potential translational targets for microbiome-based therapeutic strategies. The gene discussed is JAM2; the disease is hepatocellular carcinoma.