Lactiplantibacillus plantarum Strains LP5 and BX62 Alleviate Liver Injury of NAFLD in Rats via Regulating Hepatic Cholesterol Metabolism and Antioxidant Signaling Pathways.

Disorders of lipid metabolism and oxidative stress are pivotal factors in the advancement of non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the liver-protective effects of two Lactiplantibacillus plantarum (L. plantarum) strains, LP5 and BX62, either individually or in combined, on NAFLD in rats induced by high fat and cholesterol diet. Strain L. plantarum LP5 showed potential for modulating cholesterol metabolism, whereas L. plantarum BX62 exhibited enhanced antioxidant properties. All three intervention strategies alleviated liver injury, as evidenced by reduced hepatic lipid accumulation, intestinal permeability, inflammation, and liver injury markers. Notably, L. plantarum LP5 showed greater effects on reducing weight gain and hepatic steatosis, while L. plantarum BX62 provided additional protection against hepatic oxidative damage. Metabolic and molecular analyses suggested that the beneficial effects of L. plantarum LP5 were associated with altered bile acid homeostasis and increased expression of hepatic primary bile acid synthesis-related proteins (CYP7A1 and CYP8B1), whereas L. plantarum BX62 was associated with activation of the Nrf2-HO-1 antioxidant pathway (Nrf2, HO-1, and FTH). Furthermore, all intervention strategies activated AMPK signaling (p-AMPK/AMPK), accompanied by decreased expression of lipogenesis-related proteins (SREBP-1c, FASN, and SCD1) and increased expression of fatty acid oxidation-related proteins (PPARα and CPT1a), contributing to improved hepatic lipid metabolism. Collectively, our findings indicate that L. plantarum LP5 and L. plantarum BX62 alleviate HFHC diet-induced hepatic metabolic disturbances by complementary mechanisms involving cholesterol metabolism and antioxidant responses, highlighting their potential as dietary probiotics for supporting liver health and preventing NAFLD progression.