Laetiporus sulphureus polysaccharides mitigate colitis by reshaping the gut microbiota and regulating immune responses

Background: polysaccharides (LSP) in dextran sulfate sodium (DSS)-induced colitis, focusing on intestinal barrier restoration, immunomodulation, and gut microbiota remodeling. Methods: LSP was structurally characterized using HPLC, FTIR, and SEM analyses, revealing a heteropolysaccharide primarily composed of glucose (55.16%), galactose (16.55%), and mannose (13.52%). Experimental colitis was induced in BALB/c mice with 3% DSS, followed by oral LSP administration (200 or 400 mg/kg). Disease severity, histopathology, barrier markers, cytokine profiles, macrophage polarization, and gut microbiota composition were evaluated using biochemical assays, immunofluorescence, IHC, and 16S rRNA sequencing. Results: , Bifidobacterium, and Ruminococcus (∼2-4-fold). Conclusion: LSP exerts multi-targeted protection against colitis by reinforcing epithelial barrier function, attenuating inflammation, and reshaping gut microbial ecology. These findings highlight LSP as a promising natural therapeutic candidate for IBD. Further metabolomic and meta transcriptomic analyses are warranted to elucidate the microbial metabolites and molecular pathways mediating these protective effects.