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., Mucispirillum, Romboutsia) 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.