Obesity has been associated with a perturbed gut microbiota in both humans and mice, and this study shows that such alterations can lead to obesity-related hepatocellular carcinoma. After establishing that antibiotic treatment blocks hepatocellular carcinoma development, the authors observed that the levels of deoxycholic acid (DCA; a gut bacterial metabolite known to promote DNA damage and to be associated with carcinogenesis) increased in mice fed a high-fat diet and decreased following antibiotic treatment. Importantly, reduced DCA levels blocked hepatocellular carcinoma development, and reciprocally, DCA administration to lean mice had the opposite effect. Further analysis revealed that the main bacterial population responsible for the increased DCA production in mice fed a high-fat diet belonged to Clostridium cluster XI, operational taxonomic unit (OTU)-1105.