Low-Molecular-Weight Soluble Dietary Fiber Promotes Recovery from Cyclophosphamide-Induced Intestinal Injury: Insights from Gut Microbiota and Metabolomics

Abstract In this study, low-molecular-weight soluble dietary fiber (LMW-SDF) was prepared from sodium alginate using a recombinant mutant alginate lyase and evaluated for its ability to promote recovery from cyclophosphamide (CTX)-induced intestinal injury in mice. Oral administration of LMW-SDF significantly reduced serum lipopolysaccharide (LPS) and diamine oxidase (DAO) levels, alleviated colonic inflammation and oxidative stress, and improved epithelial barrier integrity by upregulating Claudin-1, Occludin, and ZO-1 (P < 0.05). 16S rRNA sequencing demonstrated that LMW-SDF partially restored gut microbial diversity and reshaped the gut microbiota, accompanied by alterations in the abundance of Ligilactobacillus, Lactobacillus, and norank_f_Muribaculaceae. Untargeted metabolomics indicated partial recovery of CTX-induced metabolic disturbances, particularly in tryptophan, arachidonic acid, and primary bile acid metabolism. Immunofluorescence analysis further suggested that these protective effects were associated with modulation of the TLR4/NF-κB pathway. These findings support the potential application of LMW-SDF as a dietary intervention for chemotherapy-associated intestinal injury.