Clostridium butyricum NCU-02 Alleviates Hyperlipidemia via Activating Hepatic PPARγ-LXRα-ABCA1 Pathway and Modulating the Gut microbiota

Hyperlipidemia, characterized by aberrant lipid profiles, induces fatty deposits on arterial walls, thereby markedly increasing the risk of serious cardiovascular diseases like atherosclerosis. Probiotics have recently garnered attention as a promising strategy for managing hyperlipidemia since they offer lipid-lowering benefits for the host. In this study, we isolated Clostridium butyricum NCU-02 from centenarian fecal samples and evaluated its potential to mitigate hyperlipidemia in ApoE^-/- mice fed a high-fat diet. We demonstrated that C. butyricum NCU-02 exhibited robust probiotic characteristics, including acid/bile tolerance, antibacterial activity, and enhanced growth capacity. Supplementation with C. butyricum NCU-02 significantly improved serum lipid levels, alleviated systemic inflammation, and mitigated oxidative stress. Moreover, C. butyricum NCU-02 activated the hepatic PPARγ-LXRα-ABCA1 pathway, facilitating cholesterol efflux and consequently reducing both hepatic injury markers and lipid accumulation. Furthermore, C. butyricum NCU-02 restored gut microbiota homeostasis in hyperlipidemic mice, characterized by the enhanced microbial diversity, improved intestinal barrier function, and modulated microbial composition. Notably, the increased Blautia, decreased Alistipes, and improved biochemical parameters showed significant correlation with anti-hyperlipidemic effects. These results highlight the therapeutic potential of C. butyricum NCU-02 as a probiotic intervention for hyperlipidemia, offering a multifaceted approach to lipid regulation and gut health modulation.