Seaweed polysaccharides as multifunctional biotherapeutics in modulating gut microbiome, metabolic disorders and beyond: A review.

Seaweed-derived polysaccharides-fucoidan, laminarin, alginates, ulvan, and carrageenan-are often described as promising prebiotics with potential to influence the gut-liver-brain axis. Resistant to upper gastrointestinal digestion, they reach the colon where gut microbiota ferment them into metabolites, chiefly short-chain fatty acids (SCFAs). These metabolites in turn modulate intestinal barrier integrity, immune and metabolic homeostasis, and inter-organ signaling. However, a critical caveat is that each polysaccharide type exhibits substantial structural variability in molecular weight, degree and position of sulfation, monosaccharide composition, and linkage pattern, depending on species, harvest time, and extraction method. This variability fundamentally alters fermentation kinetics and SCFA profiles, yet most studies treat these polysaccharides as uniform entities. This review critically synthesizes current in vitro and in vivo evidence and emphasizes that the therapeutic significance of seaweed polysaccharides lies in their microbiota-mediated, multi-organ actions rather than in isolated biological effects. In addition, we analyzed the main challenges for food and health applications, including variability in polysaccharide sources and extraction methods, limited bioavailability, pollution risk, and the lack of coordinated global regulations. Addressing these gaps is essential for translating promising biological activities into safe, standardized functional components and for developing these polysaccharides into functional ingredients that can modulate the gut-liver-brain axis.