Ulcerative colitis (UC) has shown a significant upward trend in global incidence and is frequently accompanied by psychiatric comorbidities such as anxiety and depression, severely impairing patients' quality of life. This study investigated the effects of inulin-derived difructose anhydride I (DFA-I) and difructose anhydride III (DFA-III) on dextran sulfate sodium (DSS)-induced UC-associated anxiety- and depression-like behavioral alterations in mice. Through oral administration, behavioral assessments, histopathology, cytokine analysis, gut microbiota sequencing, and short-chain fatty acid (SCFA) measurement, we evaluated the potential associations between DFA intervention and gut microbiota-gut-brain axis-related responses. The results suggested that DFAs, particularly 3% DFA-III, alleviated DSS-induced colonic injury and behavioral abnormalities, reduced serum levels of CORT, IL-6, and TNF-α, modulated hippocampal BDNF/p75NTR-related gene expression, and increased butyrate levels together with alterations in gut microbial composition. These findings provide preliminary evidence suggesting that inulin-derived DFAs may serve as potential prebiotic candidates for alleviating DSS-induced colitis-associated inflammatory and behavioral alterations.
