Glycosidase-Derived Arabinoxylan Hydrolyzates Attenuate Intestinal Inflammation via Restructuring the Gut Microbiota-Metabolite Axis

The highly polymeric structure and complex branching of arabinoxylan (AX) limit its immunomodulatory potential. This study investigated whether enzymatic hydrolysis using xylanase (XYN) and α-l-arabinofuranosidase (ARF) could enhance anti-inflammatory efficacy in DSS-induced colitis. Synergistic ARF-XYN treatment, yielding low-polymerization and debranched oligosaccharides, exhibited superior efficacy in ameliorating colitis symptoms, suppressing pro-inflammatory cytokines (IL-6, TNF-α, IL-1β), and restoring intestinal barrier integrity compared to native AX. Multiomics analyses revealed that ARF-XYN reshaped the gut ecosystem by enriching beneficial bacteria (Akkermansia, Faecalibaculum, Dubosiella) while suppressing pathogenic taxa (Bacteroides, Escherichia-Shigella, and Helicobacter). This microbial restructuring drove a metabolic shift characterized by increased bile acids and short-chain fatty acids, while suppressing inflammatory mediators (prostaglandin B2, histamine, quinolinic acid) and pro-inflammatory lipid metabolites (arachidonic acid, linoleic acid, and their derivatives). These findings demonstrate that precise enzymatic tailoring transforms AX into a potent functional prebiotic ingredient, offering a structure-guided prebiotic strategy for inflammatory bowel disease management through targeted microbiota–metabolite modulation.