Combined Effect of Bifidobacterium longum Postbiotics and Dietary Herbs on Ameliorating Metabolic Disturbances in Hyperlipidemic Mice

Hyperlipidemia-associated obesity is frequently accompanied by hepatic injury, bile acid dysregulation, gut microbial remodeling, and anxiety-like behavioral alterations. As emerging functional food ingredients, postbiotics and dietary herbs (DH) may provide practical dietary strategies for metabolic health management, but the most suitable postbiotic form and its compatibility with DH remain unclear. In this study, FB 3-14-derived postbiotics were first screened in vitro for cholesterol micellar binding. Inactivated bacterial cells (Postcell) exhibited the strongest cholesterol-binding capacity and were therefore selected for in vivo validation, alone or in combination with DH, in a high-fat, high-cholesterol (HFHC) mouse model. Consistently, Postcell showed superior efficacy in attenuating body weight gain, jejunal triglyceride accumulation, and hepatic dysfunction compared with other postbiotic forms. Importantly, Postcell_DH exerted broader metabolic benefits, including reductions in weight gain, food efficiency, bile acid dysregulation, and neuroinflammation. Multi-omics analysis further indicated that these effects may be mediated through remodeling of the gut microbiota and metabolome, particularly pathways involved in bile acid and tryptophan metabolism. Notably, Clostridioides and taurochenodeoxycholate-7-sulfate were negatively associated with total cholesterol (TC) and leptin, whereas Clostridium_sensu_stricto_1 and 3-Hydroxyindolin-2-1-sulfate were negatively correlated with brain inflammatory level, lipid, and bile acid-related index. This study supports a practical postbiotic–herbal combination strategy relevant to functional food and dietary supplement development for hyperlipidemia-associated metabolic disturbances.