Fusobacterium nucleatum Promotes Liver Metastasis in Colorectal Cancer by Altering Gut Microbiota and Regulating the Hepatic Immune Niche

Liver metastasis is the major cause of death in patients with colorectal cancer. However, further underlying mechanisms remain unknown. As an important modulator in the intestinal microenvironment, gut microbiota are closely linked to the initiation and progression of CRC. In this study, we investigated the contribution of Fusobacterium nucleatum to liver metastasis of CRC in mice. We found that oral administration of F. nucleatum promoted CRC liver metastasis accompanied by observable negative effects on body weight, cecum weight, and overall survival time. In addition, F. nucleatum modulated the hepatic immune niche by reducing the infiltration of CD3+ T cells and increasing the levels of tumor necrosis factor alpha . Sustaining F. nucleatum exposure, which decreased the diversity of the gut microbiota, induced an imbalance in murine intestinal flora and reshaped the intestinal flora community. In particular, the abundance of CRC promoting bacteria such as Enterococcus and Escherichia was also elevated after F. nucleatum treatment. In conclusion, our study illustrated that F. nucleatum is a mediator between the imbalance of gut microbiota and CRC liver metastasis. More importantly, F. nucleatum induced dysbiosis regulates the hepatic immune environment and promotes cancer cell colonization and survival. Therefore, restoring the healthy community of intestinal flora may be beneficial for treatment of patients with CRC.