The Synergistic Role of Sargassum horneri Fucoidan and Lactobacillus plantarum: Microbiome and Gut Barrier Restoration in Zebrafish Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by disruption of the intestinal barrier and gut microbiota imbalance, leading to significant impairment in patient quality of life. This study investigated the therapeutic efficacy of a synbiotic formulation composed of purified fucoidan from bloom-forming <i>Sargassum horneri</i> and the probiotic <i>Lactobacillus plantarum</i> in a dextran sulfate sodium (DSS)-induced zebrafish model of UC. Polysaccharides from <i>S. horneri</i> were extracted using Celluclast-assisted extraction and fractionated via DEAE anion-exchange chromatography, resulting in six fucoidan fractions. The sixth fraction (SH-F), with a molecular weight of 254 kDa, showed the highest fucose, sulfate contents, and demonstrated the highest effect on promoting <i>L. plantarum</i> growth. Structural analysis revealed that SH-F contained α-L-Fucp-(1→3), α-L-Fucp-(1→4), β-D-Galp-(1→2,3,4), α-L-Fucp-(1→3,4), and terminal α-L-Fucp residues where Fuc₁(SO₃)₁, Gal1Fuc₁(SO₃)₁, and Fuc₂(SO₃)₂ were the most common glycans. Synbiotic administration significantly attenuated DSS-induced colonic shrinkage, inhibited pro-inflammatory cytokines (IL-6, TNF-ɑ, and IL-1β), restored tight junction proteins (ZO-1, occludin), and downregulated the iNOS, COX2, and NF-κB signaling pathway in adult zebrafish. 16S rRNA gene sequencing revealed restoration of gut microbial diversity and increased abundance of beneficial bacterial taxa to improve DSS-induced UC. These findings highlight the potential synergistic effects of SH-F and <i>L. plantarum</i> as a combinatorial strategy to regulate gut inflammation and enhance epithelial barrier function, potentially offering new insights and therapeutic opportunities for UC intervention.