Development and clinical validation of Lactobacillus helveticus BGRA43: An innovative probiotic approach for MASLD

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and is closely associated with metabolic disorders such as obesity, insulin resistance, and dyslipidemia. Its prevalence continues to increase, and current management strategies rely primarily on lifestyle modification, it is necessary to develop new affordable and scientifically based interventions. Increasing evidence implicates gut microbiota dysbiosis and impaired intestinal barrier function in MASLD pathogenesis, positioning probiotics as promising therapeutic candidates. We investigated the effects of the probiotic strain Lactobacillus helveticus BGRA43 (LHBGRA43) in a preclinical diet-induced obesity model. Oral administration of LHBGRA43 significantly reduced subcutaneous adipose tissue mass and completely prevented hepatic steatosis in obese mice, as shown by histological analysis. These effects were accompanied by reduced expression of sterol regulatory element-binding protein-1c (SREBP-1c), the fatty acid transporter CD36, enzymes involved in ceramide synthesis, and pro-inflammatory markers. LHBGRA43 improved intestinal barrier integrity, as indicated by increased ZO-1 protein levels, and favorably modulated gut microbiota composition, including a reduced Firmicutes/Bacteroidota ratio, enrichment of the genera Alistipes, Acetatifactor, and Odoribacter, and decreased concentrations of branched-chain fatty acid metabolites. Based on these findings, we developed and commercialized a probiotic formulation based on LHBGRA43 intended to support MASLD management. The translational pathway progressed from preclinical validation to a post-marketing randomized controlled clinical study, which confirmed beneficial effects in patients with MASLD. Collectively, these findings support LHBGRA43 as a scientifically validated probiotic approach for improving liver health and providing a novel strategy to address a recognized gap in current metabolic disease management.