Whole-Genome-Guided Functional Characterization of Limosilactobacillus fermentum SHY0006 Reveals Hypolipidemic Activity and Improvement in Insulin Resistance

Limosilactobacillus fermentum SHY0006 was isolated from Miao sour soup, a traditional fermented food from Guizhou, China, and systematically evaluated for its safety, metabolic functionality, and stress adaptability using phenotypic assays combined with whole-genome sequencing. SHY0006 exhibited no hemolytic activity and harbored no detectable virulence-associated or acquired antibiotic resistance genes, supporting its safety profile. Functionally, SHY0006 improved lipid metabolism and insulin resistance in both cell and animal models. In hyperlipidemic mice, hepatic triglyceride accumulation was markedly reduced, accompanied by favorable modulation of serum lipid parameters, including LDL-C, HDL-C, and free fatty acids. In diabetic mice, the strain improved insulin tolerance test (ITT) performance, indicating enhanced systemic insulin sensitivity. Whole-genome analysis revealed complete biosynthetic pathways for riboflavin and folate, along with extensive carbohydrate utilization capacity, highlighting its metabolic versatility. In addition, SHY0006 exhibited strong tolerance to environmental stress, supporting its potential viability in food matrices and gastrointestinal conditions. Collectively, these findings suggest that SHY0006 is a safe and metabolically versatile probiotic candidate with potential applications in functional foods targeting metabolic health.