Impact of Dietary Interventions with Schleiferilactobacillus harbinensis Z171, Its Exopolysaccharide, and Postbiotics on Hepatic Cholesterol Metabolism in High-Fat Diet-Fed Mouse Model

Lactic acid bacteria (LAB) and their metabolic derivatives, including exopolysaccharide (EPS), as well as postbiotics (POS), exhibit considerable potential for application as healthy foods and dietary supplements for the host. Evaluating the cholesterol-lowering activities of LAB, EPS and POS, with a focus on their impact on lipid metabolism, has become a hotspot in the development of cholesterol-lowering food products. This study was designed to assess the impacts of <i>Schleiferilactobacillus harbinensis</i> Z171 and its EPS and POS on hepatic cholesterol metabolism of C57BL/6 mice fed a high-fat diet (HFD). Key biomarkers related to cholesterol synthesis, bile acid production, cholesterol transport, and the role of AMPKα activation in inhibiting cholesterol synthesis were studied. The results indicated that Z171, POS, and a high dose of EPS (400 mg/kg) significantly reduced serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) by 39.73-41.74%, 34.72-37.43, and 31.74-40.76%, respectively, while simultaneously increasing high-density lipoprotein cholesterol (HDL-C) level by 26.57-31.00%. Furthermore, histopathological analysis revealed that these interventions led to reduced fat accumulation in the liver and an improved liver morphology. Additionally, metabolomic analysis demonstrated that these interventions promoted bile acid synthesis, as evidenced by increased CYP7A1 expression, leading to enhanced cholesterol catabolism. These findings suggested that Z171, POS, and high-dose EPS may be effective in managing hypercholesterolemia by regulating cholesterol synthesis, enhancing bile acid production, and improving lipid metabolism in HFD mice. This work contributes to the understanding of the potential of LAB, POS and EPS as functional ingredients for improving metabolic health.