Divergent immunomodulatory and gut microbiota-modulating effects of Sargassum polysaccharides and oligosaccharides in delayed-type hypersensitivity mice.

Recent research has indicated that polysaccharides extracted from Sargassum (SP) possess promising activity in alleviating type I hypersensitivity reactions. However, effects of SP and Sargassum oligosaccharides (SO) on immune regulation and gut microbiota in type IV hypersensitivity remain unexplored. In this study, SP and SO were prepared and structurally characterized. SP contained high-molecular-weight fractions (866 kDa and 276 kDa), whereas SO was composed of low-molecular-weight components (3.74 kDa and 126 Da), lacked sulfate groups, and exhibited higher reducing sugar contents. The influence of SP and SO on immune regulation and the structure of gut microbial communities was examined using a mouse model of ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH). Administration of SP and SO (25 or 250 mg/kg per day for 10 days) significantly attenuated DTH responses, evidenced by a decrease in footpad edema and a lower degree of cell infiltration. While both SP and SO had limited effects on serum IgG₁ levels and splenic TGF-β production, treatment with SO at 250 mg/kg significantly reduced serum total IgG, OVA-specific IgG, and splenic IL-2 levels, while increasing IL-10 production. Notably, SO exerted the most pronounced effect in lowering IgG_2a and IFN-γ levels. Additionally, SO treatment led to distinct shifts in gut microbial profile, marked by elevated levels of Muribaculaceae, Lactobacillus, and Bacteroides. These microbial changes were accompanied by elevated concentrations of short-chain fatty acids (SCFAs). Collectively, these results indicate that SO holds potential as a functional dietary component for the alleviation of type IV hypersensitivity responses, through modulation of gut microbiota and immunomodulation.