Seaweed sulfated polysaccharides regulate the gut microbiota-mucosal barrier-innate immunity axis: structural heterogeneity, immunological evidence, and translational prospects.

Seaweed sulfated polysaccharides, fucoidan, carrageenan, ulvan, and porphyran, are structurally diverse marine glycans that modulate the gut microbiota, mucosal barrier, and innate immunity, yet the literature remains fragmented across classes, models, and processing histories. This review synthesizes evidence on their structure-function relationships, focusing on microbial enzymatic accessibility, selective fermentation, metabolite remodeling, barrier regulation, and immune signaling, while also assessing translational barriers. A systematic literature search prioritized mechanistic studies, structural analyses, animal models, human trials, and high-quality reviews. Our analysis reveals that porphyran provides the clearest microbiota-barrier coupling, fucoidan and carrageenan give the richest, but most heterogeneous, immune readouts, and ulvan is an emerging class with growing intestinal evidence. Molecular weight, sulfation pattern, and degradation history consistently shape microbial utilization and downstream effects across all classes. Disease contexts with the strongest support include inflammatory bowel disease, constipation, barrier injury, and infection-driven intestinal inflammation. Time-dependent immune shifts have been reported, but durable epigenetic memory remains unproven, and extra-intestinal evidence through gut-liver and gut-brain axes is still preliminary. We conclude that these polysaccharides are best understood as structurally defined substrates that bridge the microbiota, barrier, and immunity; future progress toward clinical translation will depend on stricter standardization, integrated mechanistic designs, and robust human data.