Marine Sulfated Polysaccharides as Multifunctional Bioactives: Implications for Gut Microbiota and Human Health

Marine macroalgae have emerged as sustainable sources of bioactive compounds, particularly sulfated polysaccharides with potential prebiotic functionality. This review examines the role of marine sulfated polysaccharides, including fucoidan, carrageenan, and ulvan, for their ability to modulate the gut microbiota and promote human health. We synthesize current evidence on how structural characteristics, such as molecular weight and degree of sulfation, influence bioaccessibility, fermentation, and potential bioavailability. The resulting metabolites play central roles in maintaining gut barrier integrity, regulating immune responses, and supporting metabolic health. In addition to functional benefits, we evaluate key challenges that limit the translation of seaweed-derived polysaccharides into food applications, including variability in composition, structural instability during processing, and safety concerns related to heavy metal accumulation and iodine content. We further discuss how extraction techniques, chemical characterization, and standardization strategies influence both efficacy and safety. Emerging approaches, such as metabolomic profiling, controlled aquaculture, and nano-enabled delivery systems, where appropriate, are highlighted as tools to enhance reproducibility and functional performance. Overall, this review provides a critical framework linking marine polysaccharide structure, gut microbiota interactions, and health outcomes, while identifying practical considerations for their incorporation into functional foods. Unlike prior reviews that treat polysaccharide structure, microbiota modulation, safety, and clinical translation as separate topics, this review integrates all four into a single structure-microbiota-safety-translation framework applied comparatively across fucoidan, carrageenan, and ulvan. Advancing these compounds as next-generation prebiotic ingredients, with evidentiary support that currently varies markedly across compounds, will require integration of food science, microbiology, and translational research to ensure consistent, safe, and clinically relevant applications.