<i>Sargassum fusiforme</i> polysaccharides modulate gut microbiota and metabolites to regulate hyperlipidemia in mice fed a high-fat diet

Obesity and its associated metabolic disorders pose a global health challenge, necessitating safe and scalable interventions. This study demonstrated that polysaccharides from <i>Sargassum fusiforme</i> (SFPS), extracted via a novel non-alcoholic precipitation method, effectively ameliorate high-fat diet (HFD)-induced obesity by remodeling gut microbiota and restoring metabolic homeostasis. Integrating multi-omics approaches, we reveal that SFPS enriches beneficial taxa like Akkermansia while suppressing obesity-linked bacteria like Actinobacteria, Erysipelotrichaceae, and Bifidobacteriaceae; modulates cholesterol metabolism through gene regulation (e.g., downregulating Srebf1 and upregulating Mt1); and enhances bile acid excretion. Notably, SFPS exhibits efficacy comparable with the well-studied fucoidan (SFF); however, its cost-effective extraction method offers superior scalability for functional food development. These findings underscore the potential of SFPS as a prebiotic agent targeting the gut-liver axis, providing mechanistic insights into natural product-based strategies for metabolic disease management. This work advances our understanding of how polysaccharides interact with the host microbiome and metabolism, advancing dietary interventions for obesity management one step further.