3'-Sialyllactose and <i>B. infantis</i> synergistically alleviate gut inflammation and barrier dysfunction by enriching cross-feeding bacteria for short-chain fatty acid biosynthesis

Ulcerative colitis (UC) poses significant threats to human health and quality of life worldwide, as it is a chronic inflammatory bowel disease. 3'-sialyllactose (3'-SL) is a key functional component of milk oligosaccharides. This study systematically evaluates the prebiotic effects of 3'-SL and its therapeutic potential in combination with <i>Bifidobacterium infantis</i> (<i>B. infantis</i>) for UC. The findings reveal that 3'-SL and <i>B. infantis</i> synergistically mitigate intestinal inflammation and barrier dysfunction by promoting the production of short-chain fatty acids (SCFAs) through cross-feeding mechanisms among gut microbiota. Individually, 3'-SL, <i>B. infantis</i>, and the synbiotic treatment all effectively alleviated UC symptoms, including reduced weight loss, improved disease activity scores, and prevention of colon shortening. Histopathological and immunofluorescence analyses further demonstrated that the synbiotic treatment significantly ameliorated colonic injury, enhanced barrier function, restored goblet cell counts, increased glycoprotein content in crypt goblet cells, and upregulated the expression of tight junction proteins (ZO-1, occludin, and claudin-1). Notably, the synbiotic treatment outperformed the individual components by better restoring gut microbiota balance, elevating SCFA levels, and modulating serum cytokine profiles, thereby reducing inflammation. These findings provide mechanistic insights into the protective effects of the synbiotic and underscore its therapeutic potential for UC and other intestinal inflammatory disorders.