Comparative immunomodulatory and gut microbiota-regulating effects of macroalgal polysaccharides in cyclophosphamide-induced immunosuppressed mice.

Polysaccharides derived from macroalgae exhibit potent immunomodulatory and gut-regulatory activities; however, comprehensive comparisons of their differential bioactivities remain scarce. This study systematically evaluated the immunomodulatory potential of structurally distinct polysaccharides extracted from Sargassum fusiforme (SP) and Ulva lactuca (UP) in a cyclophosphamide (CTX)-induced immunosuppressed mouse model. Structural analyses revealed that SP consisted mainly of fucose (64.5%) and galactose (20.4%) with molecular masses of 95.6 and 1.4 kDa, while UP was primarily composed of glucose (60.4%) and rhamnose (34.1%) with molecular masses of 908.2, 10.9, and 1.2 kDa. Both polysaccharides exhibited characteristic sulfate absorption peaks. Oral administration of SP or UP (125 and 250 mg/mL) for 14 days significantly alleviated CTX-induced reductions in thymus and spleen indices and mitigated lymphoid tissue injury. Treatments restored splenocyte populations-including CD8+ T cells and B220+ B cells-increased serum IgG levels and enhanced splenocyte viability. SP and UP also promoted lipopolysaccharide (LPS)-induced cytokine production, notably IL-2, IFN-γ, IL-6, and TNF-α, with SP showing stronger immunostimulatory effects, particularly in B-cell restoration and cytokine secretion. Gut microbiota profiling revealed that both polysaccharides ameliorated CTX-induced dysbiosis by enriching Lactobacillus, reducing Desulfovibrio, and increasing short-chain fatty acid levels. Collectively, these findings demonstrate that SP and UP enhance immune function and modulate gut microbiota in immunosuppressed mice, with SP exerting superior activity. This first comparative study provides mechanistic insight and supports their potential as functional food supplements or immunotherapeutic adjuvants.