Screening Cholesterol-Lowering <i>Lactiplantibacillus plantarum</i> through <i>In Vitro</i> Experiments, Whole Genomics Analysis, and <i>In Silico</i> Approaches: From the Perspective of Bile Salt Hydrolase and Cholesterol

Hypercholesterolemia is a cardiovascular condition resulting from elevated cholesterol levels. This study screened seven <i>Lactiplantibacillus plantarum</i> strains with efficient cholesterol (CHOL)-lowering abilities and investigated the mechanisms of CHOL degradation. HPLC analysis indicated that <i>L. plantarum</i> D5205 had high bile salt hydrolase (BSH) activity with a bile salt metabolism rate of 31.65% ± 0.43%, while <i>L. plantarum</i> C4507 excelled with a CHOL metabolism rate of 61.12% ± 0.32%. Microscopic analysis revealed that these strains reduced CHOL mainly through extracellular binding and intracellular metabolism. The genomic analysis indicated that the BSH and transporter protein genes were strongly associated with the CHOL metabolism capabilities of these strains. The molecular docking and molecular dynamics simulation analysis revealed the binding mechanism between sodium taurocholate and BSH. This study provides a method for screening CHOL-lowering lactic acid bacteria and uncovers their potential mechanisms for reducing CHOL levels.