Probiotic Properties of Pediococcus acidilactici Z123 and its Intervention Effects and Mechanisms on...

The intervention effects and underlying mechanisms of Lactobacillus strains against hypercholesterolemia in mice have been extensively documented. However, fewer studies have focused on the cholesterol-lowering potential and the corresponding metabolic regulatory mechanisms of Pediococcus acidilactici. In the present study, we first characterized the in vitro probiotic properties of a novel lactic acid bacterial strain, Pediococcus acidilactici Z123 (P. acidilactici Z123), which exhibited prominent cholesterol-lowering activity. Subsequently, intragastric administration of P. acidilactici Z123 was carried out in a mouse model of high-fat diet-induced hypercholesterolemia to assess its intervention effect and elucidate the underlying molecular mechanisms. The results revealed that P. acidilactici Z123 possessed desirable probiotic characteristics such as auto-aggregation, adhesion ability, and gastrointestinal fluid tolerance, and showed good biosafety, inculding antibiotic susceptibility and no hemolytic activity. In vivo results demonstrated that supplementation with P. acidilactici Z123 effectively alleviated excessive body weight gain and reduced visceral fat accumulation, improved serum lipid profiles, and ameliorated the histological morphology of the liver and epididymal adipose tissue. Untargeted metabolomics indicated that P. acidilactici Z123 exerted a significant regulatory effect on lipolysis in adipocytes, PPAR and AMPK signaling pathways, primary bile acid metabolism, bile secretion, tryptophan metabolism, etc. Notably, such metabolic regulation was further verified at the transcriptional level. Quantitative reverse transcription PCR (qRT-PCR) analysis revealed that P. acidilactici Z123 intervention could inhibit cholesterol synthesis by downregulating the expression of Hmgcr and Srebf1, and upregulating the expression of Prkaa1. Meanwhile, it also elevated the expression of genes related to fatty acid oxidation (Cpt1a, Pparα) and bile acid synthesis (Cyp7a1). The present findings will provide valuable theoretical evidence for the development and application of novel functional probiotic products with lipid-regulating properties.