Metabolomics and proteomics analysis elucidate the regulation of selenium uptake and metabolism by selenite via glutathione S-transferase in fermented goat milk.

Lactic acid bacteria exhibit the capability to bioconvert selenite into selenomethionine through nonspecific incorporation into proteins via methionine substitution. Nevertheless, the dynamic mechanisms of selenium metabolism in fermented goat milk remain unclear, limiting the development of selenium-enriched dairy products. This investigation systematically analyzes the metabolic changes in fermented goat milk under selenite concentration gradients. Metabolomics identified L-arginine and selenomethionine as significantly altered metabolites, with pathway enrichment analysis revealing selenite-mediated arginine and glutathione metabolism, and elevated selenite concentrations decreased L-arginine levels. Proteomics identified α-lactalbumin and β-casein as differentially expressed proteins, enriched in cholesterol and galactose metabolism. The molecular mechanism demonstrated that selenite promoted the accumulation of L-glutathione oxidized by activating glutathione S-transferase while suppressing β-galactosidase expression, leading to significant reductions in lactose (9.16-3.86 μg g). Multi-omics integration revealed that selenite regulated the fermentation system through metabolite response-protein expression, establishing a theoretical foundation for the development of functional selenium-enriched products.