Rifaximin Alleviates MASH by Suppressing Deoxycholic Acid-Triggered Macrophage-Hepatocyte Dialogue

This study investigates the therapeutic mechanism of rifaximin, an oral non systemic antibiotic, in the context of MASH progression and its modulation by bile acid signaling. Our preliminary data indicated that while rifaximin significantly ameliorates MASH features, deoxycholic acid (DCA), a secondary bile acid and potent S1PR2 agonist reverses these beneficial effects.

To systematically dissect the specific cellular populations involved, we performed single-nucleus RNA sequencing (snRNA-seq) and bulk RNA-seq on liver tissues from mice under various conditions, including HFF-induced MASH, rifaximin treatment, and rifaximin treatment supplemented with DCA reconstitution. The snRNA-seq analysis primarily focused on the hepatic immune landscape, specifically the dynamics of monocyte-derived macrophages (MoMFs).