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

Ning Su,Shiwei Han,Zhengyang Li,Xiaoyu Ling,Lingqing Kong,Dafeng Song

Published 2025 in Applied and Environmental Microbiology

ABSTRACT

ABSTRACT Hyperlipidemia complications caused by obesity are a hot issue threatening human health worldwide, and there is an urgent need to explore low-toxicity health foods for intervention. Sargassum fusiforme polysaccharides (SFPS) display cholesterol-lowering properties, but the underlying mechanism has not been elucidated. This study investigates the mechanisms by exploring changes in gut microbiota composition, gene expression, and metabolites in mice fed a high-fat diet after intervention with S. fusiforme fucoidan (SFF) and SFPS through 16S rRNA sequencing, transcriptomics, and non-targeted metabolomics. The experimental findings indicated that SFPS markedly enhanced the abundance of Akkermansia while concurrently reducing the levels of Actinobacteria, Erysipelotrichaceae, Bifidobacteriaceae, and Peptostreptococcaceae. This was achieved by upregulating the expression of Mt1, Prlr, and slc25a21 and downregulating SREBP-1, thereby inhibiting the cholesterol metabolism pathway. These changes resulted in increased hepatic production and fecal excretion of bile acids and reduced hepatic cholesterol. Our results shed light on the mechanisms behind the cholesterol- and lipid-lowering effects of SFPS, suggesting its potential as a therapeutic agent for hypercholesterolemia. IMPORTANCE Obesity and its associated metabolic disorders pose a global health challenge, necessitating safe and scalable interventions. This study demonstrated that polysaccharides from Sargassum fusiforme (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. Obesity and its associated metabolic disorders pose a global health challenge, necessitating safe and scalable interventions. This study demonstrated that polysaccharides from Sargassum fusiforme (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.

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