Lactobacillus Fermentum MCC2760 Mitigates Oxidized Oil-Induced Metabolic Dysfunction and Gut-liver axis Perturbations: A Two-Generation Study in rats.

Dietary intake of oxidized oil is increasingly recognized as a key contributor to metabolic dysfunction. In this study, we evaluated the protective effects of Lactobacillus fermentum MCC2760 (LF) against oxidized oil-induced metabolic dysfunction across two generations in rats. Female Wistar rats were fed AIN-76 diets containing native or thermally oxidized sunflower oil (SFO) and canola oil (CNO), with or without LF supplementation (10⁹ CFU/day), and the F2 generation was maintained on corresponding diets. Biochemical parameters including lipid profile, oxidative stress (OS) markers (lipid peroxides, protein carbonyls), antioxidant defense enzymes (catalase, SOD, GR, GPx, GST), inflammatory mediators (PGE2, LTB4, TNF-α, MCP-1, IL-1β, IL-6), transcription factors (NF-κB, Nrf2), organ function enzymes (SGOT, SGPT, CK-MB, CK-NAC, ALP) and fecal microbiome were assessed. Consumption of oxidized oils, irrespective of fatty acid composition, significantly disrupted lipid homeostasis, increased OS, reduced antioxidant enzyme activities and Nrf2 activity, and enhanced NF-κB activity, leading to elevated inflammatory mediators. Oxidized oil intake also increased serum markers of hepatic and cardiac injury, and induced gut dysbiosis. However, daily administration of LF significantly attenuated these metabolic disturbances by improving lipid homeostasis, antioxidant defenses, and inflammatory balance, NF-κB/Nrf2 activities, and gut microbial composition. These protective effects were consistently observed in both F1-mothers and F2 offspring, supporting metabolic resilience across generations. Overall, these findings support the potential of probiotic LF as a functional dietary strategy for mitigating oxidized oil-induced metabolic dysfunction by improving lipid homeostasis, modulating NF-κB/Nrf2 activities, and promoting gut microbial balance, with findings consistent with the involvement of the gut-liver axis.