**Background:** Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is a chronic inflammatory condition of the intestinal tract with increasing global prevalence. Current treatments (5-ASA, biologics, immunosuppressants, corticosteroids) have limited remission rates (15%–44.9%) and significant adverse events. Anthocyanins (ACNs), abundant in blackcurrant (BC), have shown gut health benefits, but studies on whole BC (rather than extracts) in colitis models are lacking. This study aimed to evaluate whether whole BC powder alleviates DSS-induced colitis in mice.
**Methods:** Five-week-old male C57BL/6J mice were divided into three groups (n=8/group): Vehicle (no DSS), DSS (3% DSS in drinking water for 6 days), and DSS+BC (same DSS protocol plus daily oral BC powder at 150 mg/mice/day, equivalent to 7.5 g/kg BW, total ACN 165 mg/kg BW). Colitis was monitored daily using the disease activity index (DAI; scores for body weight loss, stool consistency, bloody stools). After sacrifice, colon length and weight were measured. Histological damage was assessed via H&E staining (epithelium loss, crypt damage, goblet cell depletion, inflammatory cell infiltration; each scored 0–3). Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in serum and colon tissue were quantified by ELISA. mRNA expression of inflammatory genes (Tlr-4, Nf-κb, iNOS, Cox-2, Tnf-α, Il-1β, Il-6, Mcp-1), tight junction proteins (Zo-1, Occludin), and mucins (Muc-1, Muc-2, Muc-3) was measured by qRT-PCR (normalized to GAPDH, 2−ΔΔCt method). Protein expression of p-p65, p65, iNOS, and COX-2 was assessed by Western blotting (normalized to β-actin). Gut microbiota was analyzed by 16S rRNA sequencing (V3–V4 region) using QIIME2 and NCBI BLAST. Statistical significance was determined by one-way ANOVA with Duncan's post hoc test (p<0.05).
**Key Results:** BC did not prevent DSS-induced body weight loss but significantly improved other clinical symptoms. Colon length in the DSS group was 4.73±0.66 cm (29.9% shorter than Vehicle: 6.75±0.33 cm), while the DSS+BC group showed significant restoration to 5.70±0.42 cm. The colon weight-to-length ratio was also significantly reduced in the DSS+BC group. Histological damage scores were significantly lower in the DSS+BC group compared to DSS alone, with reduced epithelial erosion, goblet cell depletion, crypt destruction, and inflammatory cell infiltration. Serum TNF-α was significantly elevated in DSS (7.88±1.28 pg/mL) vs Vehicle (1.93±0.58 pg/mL) and significantly reduced in DSS+BC (5.70±1.07 pg/mL). Serum IL-6 was elevated in DSS (2.92±1.13 pg/mL) vs Vehicle (0.54±0.05 pg/mL) but not significantly reduced by BC (3.02±0.51 pg/mL). Serum IL-1β showed no significant differences. In colon tissue, TNF-α was significantly higher in DSS (65.05±22.26 pg/μg protein) vs Vehicle (28.75±25.70 pg/μg protein) and significantly reduced in DSS+BC (37.30±17.13 pg/μg protein). Colon IL-1β was significantly elevated in DSS (37.58±3.64 pg/μg protein) vs Vehicle (2.85±0.71 pg/μg protein) and significantly reduced in DSS+BC (25.30±4.97 pg/μg protein). Colon IL-6 showed no significant differences. BC downregulated DSS-induced mRNA expression of Tlr-4, Nf-κb, iNOS, Cox-2, Tnf-α, Il-1β, Il-6, and Mcp-1, and upregulated expression of Zo-1, Occludin, Muc-1, Muc-2, and Muc-3. BC inhibited DSS-induced phosphorylation of NF-κB p65 and reduced protein expression of iNOS and COX-2. Gut microbiota analysis showed no significant differences in α-diversity (ASV: Vehicle 116.00±32.33, DSS 106.80±9.36, DSS+BC 125.20±36.53; Chao1: Vehicle 117.61±32.30, DSS 108.66±11.33, DSS+BC 127.79±37.95). BC modulated β-diversity and altered microbial composition: at the phylum level, BC reversed DSS-induced decreases in Firmicutes and Actinobacteria and increases in Bacteroidetes and Verrucomicrobia. At the genus level, BC decreased Bacteroides and increased Ligilactobacillus compared to DSS. At the species level, BC decreased colitis-associated Bacteroides acidifaciens and increased recovery-phase-associated Bacteroides caecimuris and Mucispirillum schaedleri.
**Clinical Implications:** This study provides preclinical evidence that whole BC powder, at a dose roughly equivalent to less than two cups of fresh BC per day in humans, can attenuate DSS-induced colitis through multiple mechanisms: suppression of the NF-κB inflammatory pathway, enhancement of intestinal barrier integrity (tight junction proteins and mucins), and favorable modulation of gut microbiota composition. These findings support the potential of whole BC as a natural dietary intervention for UC management. However, the study is limited by its animal model design, relatively small sample size (n=8/group for most outcomes, n=5 for microbiota), and the lack of a dose-response assessment. Further research is needed to confirm these effects in human clinical trials and to elucidate the precise mechanisms by which specific BC anthocyanins and their metabolites interact with the gut microbiome and host immune system.