Almond-Derived Peptide Fraction Alleviates DSS-Induced Colitis with Associated Anti-Inflammatory, Antioxidant, and Barrier-Restorative Effects

Almond-derived peptide fractions (APs) represent a promising yet underexplored class of plant-based bioactive compounds for ulcerative colitis (UC) management. This study investigated the protective effects of APs against dextran sulfate sodium (DSS)-induced colitis in male BALB/c mice using integrated 16S rRNA sequencing and transcriptomic analysis. Mice received low-dose (200 mg/kg) or high-dose (400 mg/kg) APs during 7-day DSS administration. Both doses significantly attenuated body weight loss, disease activity index, colon shortening, and histopathological damage. Compared with the DSS group, low-dose and high-dose APs reduced disease activity index by 65.9% and 52.4%, increased colon length by 30.0% and 26.5%, decreased histopathological scores by 39.6% and 55.1%, and lowered colonic myeloperoxidase activity by 13.9% and 34.1%, respectively. APs also modulated inflammatory cytokines, improved mucus-barrier-related indices, and enhanced continuous ZO-1 localization at epithelial junctions. Additionally, 16S rRNA sequencing indicated that AP treatment was associated with altered genus-level microbiota profiles after DSS exposure, including changes in Ligilactobacillus, Escherichia-Shigella, and Parabacteroides-related taxa. Transcriptomic analysis suggested dose-associated response patterns: low-dose APs were associated with broader immune-related transcriptional changes, whereas high-dose APs were more closely associated with extracellular matrix organization, focal adhesion, and genes enriched in the PI3K-Akt signaling pathway. These findings support the protective effects of APs in DSS-induced acute colitis and suggest potential associations among microbiota alterations, host transcriptional responses, and mucosal repair.