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 <i>Enterococcus</i> 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, <i>E. lactis</i> 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.