Fig. 7

The underlying mechanisms by which the gut microbiome and its metabolites influence hepatocarcinogenesis and progression. Dysbiosis and a leaky gut facilitate hepatocarcinogenesis and progression through distinct mechanisms. Microbial-derived LPS can worsen liver inflammation and fibrosis and favor hepatocyte proliferation in a TLR4-dependent manner. DCA induces DNA damage and the SASP in HSCs and synergizes with LTA to weaken the anti-tumor activity of CD8+ T cells. Moreover, DCA downregulates the accumulation of CXCR6+ NKT cells in the hepatic tumor microenvironment, which is conducive to hepatic tumor growth