Physicochemical characteristics and therapeutic mechanisms of Sargassum horneri-derived soluble dietary fiber in cyclophosphamide-induced intestinal damage via gut microbiota and metabolic modulation

In this study, soluble dietary fiber (SDF) was extracted from Sargassum horneri via enzymatic hydrolysis and evaluated for therapeutic efficacy in male ICR mice (5–6 weeks, 17–18 g) with intestinal injury induced by cyclophosphamide (CTX; 80 mg/kg/day intraperitoneal injection for 5 days). Animals received daily intragastric gavage of SDF at low- (250 mg/kg), medium- (500 mg/kg), or high-dose (1000 mg/kg) concentrations for 7 days. Biochemical assays demonstrated that SDF enhances antioxidant capacity in colon tissues and reduces serum lipopolysaccharide (LPS) levels ( P  < 0.05). The up-regulation of tight junction proteins (Claudin-1, Zonula Occludens-1, P  < 0.05) further confirmed the reinforcement of the intestinal barrier. Untargeted metabolomics revealed that SDF restores CTX-induced metabolic disorders by modulating the kynurenine pathway, optimizing histidine metabolism, and restoring glycerophospholipid homeostasis. Notably, 16S rRNA sequencing indicated that SDF induces significant shifts in microbial ecology, characterized by increased probiotics ( norank_f__Muribaculaceae , P  < 0.05; Bacteroides , P  < 0.05; Alloprevotella , P  < 0.01). These findings highlight the intricate interplay between microbiota and metabolome in SDF-mediated intestinal protection, offering novel insights for developing functional foods to combat chemotherapy-associated gut toxicity.