2. Academic Validation
  3. Impact of elobixibat on liver tumors, microbiome, and bile acid levels in a mouse model of nonalcoholic steatohepatitis

Impact of elobixibat on liver tumors, microbiome, and bile acid levels in a mouse model of nonalcoholic steatohepatitis

  • Hepatol Int. 2023 Dec;17(6):1378-1392. doi: 10.1007/s12072-023-10581-2.
Yoshiaki Sugiyama 1,  Kenta Yamamoto 1,  Takashi Honda 2,  Asuka Kato 1,  Hisanori Muto 1,  Shinya Yokoyama 1,  Takanori Ito 1,  Norihiro Imai 1,  Yoji Ishizu 1,  Masanao Nakamura 1,  Tomomi Asano 3,  Atsushi Enomoto 4,  Kei Zaitsu 5,  Masatoshi Ishigami 1,  Mitsuhiro Fujishiro 6,  Hiroki Kawashima 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya, 466-8550, Japan.
  • 2 Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya, 466-8550, Japan. [email protected].
  • 3 College of Human Life and Environment, Kinjo Gakuin University, 2-1723 Omori, Moriyama-Ku, Nagoya, 463-8521, Japan.
  • 4 Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
  • 5 Multimodal Informatics and Wide-Data Analytics Laboratory (MiWA-Lab.), Department of Computational Systems Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, 930 Nishi Mitani, Kinokawa, Wakayama, 649-6493, Japan.
  • 6 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
PMID: 37666952 DOI: 10.1007/s12072-023-10581-2
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 the serum and hepatic bile acid levels. This study aimed to investigate the impact of these factors on liver tumor.

Methods: C57BL/6J mice received a one-time intraperitoneal injection of 25-mg/kg 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 with elobixibat showed fewer liver tumors. The total serum bile acid levels, including free, tauro-conjugated, glyco-conjugated, and tauro-α/β-muricholic acids in the liver, were noticeably reduced following elobixibat treatment. 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.

Keywords

Diethylnitrosamine; Distal ileum; Fatty liver; Fibrosis; Gram-negative bacteria; Gram-positive bacteria; High-fat diet; Hypoxanthine guanine phosphoribosyl transferase; Ileal bile acid transporter; Verrucomicrobiota.

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