Intratumor sp. drives DEN-induced hepatocellular carcinoma progression by modulating gut microbiota and angiogenesis.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide with challenging clinical treatment. Accumulating evidence demonstrates that gut dysbiosis promotes HCC progression, and intratumoral bacteria play an essential role in carcinogenesis by modulating the tumor immune microenvironment. However, the microbiome within liver tumor tissues remains poorly characterized. In this study, we investigated the intratumoral microbiota of HCC and identified a specific bacterial taxon, sp. , that was enriched in tumor tissues. We found that sp. promoted HCC development partially by inducing vascular endothelial growth factor (VEGF) expression and promoting angiogenesis. Moreover, sp. induced gut dysbiosis in HCC model, characterized by an increased abundance of pro-inflammatory bacteria and a reduction in short-chain fatty acids (SCFA) producing bacteria. Furthermore, administration of sp. introduced intestinal inflammation and permeability. Our results provided evidences for the cross-talk between the sp. and HCC progression, and suggested the potential prognostic and therapeutic value of the sp. .