Figure 1. Model for obesity-associated liver cancer driven by the gut microbiome. Obesity is associated with increased risk for various cancers, but the mechanisms underlying the greater risk are unclear. As reported in Yoshimoto et al., obesity appears to drive the development of hepatocellular carcinoma (HCC) through the microbiome.

[a] According to the proposed model, obesity results in changes in the gut microbiota that lead to increased levels of deoxycholic acid. [b] Molecules of this DNA-damaging bile acid travel via enterohepatic circulation to the liver and induce the senescence-associated secretory phenotype in hepatic stellate cells. [c] Inflammatory factors released by the senescent hepatic stellate cells promote malignant transformation in nearby hepatocytes, which leads to tumor formation and HCC.