This study investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and *Limosilactobacillus reuteri* in a murine model of colitis. The synbiotic synergistically protects against intestinal inflammation and barrier dysfunction by enriching *Bacteroides acidifaciens*, which promotes pentadecanoic acid (C15:0) synthesis. The synbiotic, *B. acidifaciens*, and C15:0 each suppress inflammation and enhance tight junctions by inhibiting NF-κB activation. Reduced *B. acidifaciens* and C15:0 levels are observed in human UC patients and LPS-induced intestinal inflammation in pigs. These findings highlight the therapeutic potential of the synbiotic, *B. acidifaciens*, and C15:0 for UC and other intestinal inflammatory disorders.
