A Rushan Acid Whey-Derived Limosilactobacillus fermentum A001-A-08 Attenuates Lipid Accumulation in...

Rushan acid whey is an underutilized by-product of a traditional fermented dairy food and may contain probiotic lactic acid bacteria. This study screened cholesterol-lowering strains from Rushan acid whey and evaluated Limosilactobacillus fermentum A001-A-08 for functional traits, preliminary safety, and lipid-lowering potential in high-fat-diet-induced zebrafish. A001-A-08 showed cholesterol removal, bile salt hydrolase activity, acid/bile/simulated gastrointestinal tolerance, auto-aggregation, gamma-hemolysis, and a mostly susceptible antibiotic profile. A 10⁶ CFU/mL bath concentration maintained larval survival, heart rate, and morphology and enabled intestinal localization during the observation period. In high-fat zebrafish, A001-A-08 reduced Oil Red O-stained lipid accumulation, improved hepatic morphology, lowered TC and TG, and increased HDL-C. Transcriptomic, metabolomic, qRT-PCR, and 16S rRNA sequencing analyses indicated that these phenotypic changes were associated with alterations in lipid transport, lipoprotein assembly, bile acid-related metabolism, selected metabolite features, and gut microbial composition. These findings support A001-A-08 as a promising Rushan acid whey-derived probiotic candidate, while genome-level safety assessment, mammalian oral-administration studies, and food-matrix validation remain necessary before functional-food application.