Impact of Elobixibat on Liver Tumors, Microbiome and Bile Acid Levels in a Mouse Model of Nonalcoholic Steatohepatitis

Abstract

Abstract Background Elevated bile acid levels have been associated with liver tumors in fatty liver. Ileal bile acid transporter inhibitors may inhibit bile acid absorption in the distal ileum and increase bile acid levels in the colon, potentially decreasing serum and hepatic bile acids. This study investigated the impact of these factors on tumors. Methods C57BL/6J mice received a one-time intraperitoneal injection of 25 mg/kg of diethylnitrosamine. They were fed a choline-deficient high-fat diet for 20 weeks starting from 8 weeks of age, with or without elobixibat (EA Pharma, Tokyo, Japan). Results Both groups showed liver fat accumulation and fibrosis, with no significant differences between the two groups. However, mice treated with elobixibat showed fewer liver tumors. The total serum bile acid levels, including free-/tauro-/gly- conjugated bile acids and tauro-α/β-muricholic acids in the liver, were noticeably reduced with elobixibat. The proportion of gram-positive bacteria in feces was significantly lower in the group treated with elobixibat (5.4%) than in the group without elobixibat (33.7%). Conclusion Elobixibat suppressed tumor growth by inhibiting bile acid reabsorption and decreasing total bile acid and primary bile acid levels in the serum and liver. Additionally, the presence of bile acids in the colon may have led to a significant reduction in the proportion of gram-positive bacteria, potentially resulting in decreased secondary bile acid synthesis.