Genomic Characterization, Safety Assessment, and Probiotic Potential of a Novel Human-Derived Enterococcus lactis IOBRA9746

Probiotic strains exhibiting bile salt hydrolase (BSH) activity represent a promising therapeutic strategy for ameliorating metabolic disorders via targeting the gut–liver axis. Herein, we characterized a newly isolated human-derived Enterococcus strain and investigated its therapeutic potential. Genomic analysis confirmed its safety profile, while in vitro assays demonstrated potent BSH activity. Subsequently, C57BL/6J mice fed a high-cholesterol diet were orally administered this strain over an eight-week intervention period. Although the treatment did not significantly reduce serum cholesterol levels, a marked reduction in hepatic lipid droplet accumulation was confirmed by H&E and Oil Red O staining. Mechanistically, the strain’s potent BSH activity likely modulates bile acid metabolism within the gut–liver axis, thereby specifically inhibiting hepatic lipid deposition. Comprehensive histopathological examination of major organs revealed no signs of toxicity, affirming its excellent in vivo safety profile. In summary, E. lactis IOBRA9746 constitutes a safe and BSH-active probiotic candidate, whose primary beneficial effect lies in directly alleviating hepatic lipid accumulation independent of systemic cholesterol modulation. These findings highlight its potential as a novel liver-targeted intervention for preventing metabolic diseases induced by suboptimal dietary patterns.