Intratumor Rhodococcus sp. B513 drives DEN-induced hepatocellular carcinoma progression by modulating gut microbiota and angiogenesis

Abstract

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, Rhodococcus sp. B513, that was enriched in tumor tissues. We found that Rhodococcus sp. B513 promoted HCC development partially by inducing vascular endothelial growth factor (VEGF) expression and promoting angiogenesis. Moreover, Rhodococcus sp. B513 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 Rhodococcus sp. B513 introduced intestinal inflammation and permeability. Our results provided evidences for the cross-talk between the Rhodococcus sp. B513 and HCC progression, and suggested the potential prognostic and therapeutic value of the Rhodococcus sp. B513.