MOA demonstration #4 【Gut-Liver Axis】｜Evaluation of the efficacy of a compound in the treatment of MASH via the Gut-Liver Axis using STAM™ mice
Today, we introduce the pre-clinical studies in MASH drug development targeting Gut-Liver axis.
In MASH patients, changes in the microbiome and increased intestinal permeability (Leaky Gut) have been observed (Lixin et al., Hepatology, 2012; Jay et al., CMGH, 2015).
In fact, analyses in mouse models have shown that dysfunction of the gut-liver axis, such as increased intestinal permeability, bacterial overgrowth and enterotoxemia, contribute to the progression of inflammation and fibrosis in the liver. Therefore, treatment and prevention studies of MASH are underway, focusing on the Gut-Liver axis.
STAM™ mouse is a MASH-hepatoma model that exhibits dysbiosis characterized by increased Atopobium spp., Bacteroides spp., Bacteroides vulgatus, Bacteroides acidifaciens, Bacteroides uniformis, Clostridium cocleatum, Clostridium xylanolyticum and Desulfovibrio spp (Guoxiang X et al, Oncotarget , 7, 19355-19366, 2016). STAM™ mouse are the only MASH liver cancer models with dysbiosis that have been reported to date that reproduce the pathology of MASH liver cancer, and this model can be used to evaluate a wide range of conditions, from fatty liver to liver cancer. becomes possible. In fact, it has been reported that FMT and insulin administration suppress carcinogenesis through improving intestinal flora (Soeda K et al, Nat Commun., 14, 6584, 2023).
In previous drug efficacy evaluations related to the Gut-Liver axis, STAM™ mice have been used to evaluate test substances such as Kampo, fecal microflora transplants (FMT), bacterial consortia, and functional materials.
Below is a list of publications for the MASH and MASH-HCC treatment or preventive efficacy evaluation study on Gut-Liver axis related MOAs for your reference.
■Nine-Strain Bacterial Consortium：Pinheiro I et al., Biomedicines. 2022 May 20;10(5):1191.
■Kampo (daisaikoto): Ishizawa S et al., Gene. 2022 Dec 20;846:146856.
■beta-glucan: Preethy S et al., BMJ Open Gastroenterol. 2022 Sep;9(1):e000985.
■FMT / Insulin: Soeda K et al.,Nat Commun. 2023 Oct 18;14(1):6584.
■Kampo (Bofutsushosan):Nishiyama M et al., Pharmacological Research – Modern Chinese Medicine, 2024, Volume 11, 100440
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