Administration with Isomalto-Oligosaccharides and Galacto-Oligosaccharides at Distinct Stages of Ulcerative Colitis Progression Demonstrate Enhanced Treatment Efficacy

The biological effects of nondigestible oligosaccharides in colitis remain unclear due to limited studies on their structure-specific and stage-dependent effects. Using a dextran sulfate sodium-induced ulcerative colitis (UC) model in C57BL/6J mice, we investigated the stage-specific effects and potential mechanisms of galacto-oligosaccharides (GOS) and isomalto-oligosaccharides (IMO) during disease progression. IMO supplementation in the prevention stage enhanced microbial α-diversity, whereas GOS reduced the abundance of beneficial bacteria (e.g., <i>Mucispirillum</i>, <i>Romboutsia</i>) and inhibited taurine biosynthesis. In contrast, GOS showed beneficial potential in the active stage by upregulating genes linked to mucosal (Muc1), immune (Slc6a4, IL-22), and mechanical (Fabp2, Ang4) barriers. A staged intervention─IMO in the prevention phase followed by GOS during the active phase─was more effective than coadministration, reducing disease activity and increasing mucin and E-cadherin expression. These findings highlight the synergistic effects of timing and oligosaccharide structure specificity, offering insights into precision nutritional strategies in UC management.