rW27 IgA alleviates Enterococcus faecalis-promoted CDAHFD-induced MASH in mice by attenuating the liver fibrosis

Abstract The pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) is not well understood, and effective antifibrotic therapies are still lacking. Gut-liver interactions play a critical role in MASH progression. Fecal analysis of ten MASH patients and twelve healthy donors revealed a significant enrichment of Enterococcus faecalis in the MASH patients. Oral gavage of E. faecalis exacerbated liver fibrosis in a mouse model of MASH induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Recombinant W27 (rW27) IgA, a mouse-derived monoclonal antibody, strongly binds to E. faecalis and potently inhibits its growth in vitro. Furthermore, the oral administration of rW27 IgA to E. faecalis-colonized MASH mice significantly reduced liver fibrosis by suppressing E. faecaliscolonization and restoring the gut microbiota. These results suggest a new therapeutic approach for MASH that involves the oral administration of rW27 IgA to inhibits the colonization of pathogenic E. faecalis, restores gut microbiota, and attenuates liver fibrosis.