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Co-authored Paper by Researcher Matsumoto and Researcher Miura of the Translational Research Business Unit Published in Gut Pathogens

2026.04.09

Cross-organ multi-omics profiling of microbiome and metabolome along the gut-liver axis in MASH model mice induced by western diet and MC4R knockout

Publication
Published Date: April 1, 2026

With the rising prevalence of metabolic dysfunction-associated steatohepatitis (MASH), there is an increasing global need for effective therapeutics. However, the role of the gut–liver axis in MASH pathogenesis remains insufficiently understood. In this study, we applied microbiome and metabolomic analyses to a Western diet (WD)-fed Melanocortin 4 receptor-knockout (MC4R-KO) mouse model, which have a high translational relevance as MASH model, to characterize changes related to the gut–liver axis. We observed an increase in Desulfovibrionaceae and Bacteroides, as also reported in patients with MASH and a decrease in Muribaculaceae and Allobaculum. These changes were correlated with MASH-related endpoints including hepatic lipid accumulation, inflammation and fibrosis. We also found reduced free fatty acids and monoglycerides in the intestines, increased triglyceride and diglyceride levels in the liver, and elevated plasma taurine-conjugated bile acids accompanied by reduced hepatic transport of bile acids. These findings suggest the high translational relevance of this mouse model and indicate the potential utility of targeting the gut-liver axis in MASH drug discovery.

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