Saccharomyces cerevisiae and mannan oligosaccharide alleviate adolescent dextran sodium sulfate-induced ulcerative colitis in early-life antibiotic-exposed mice through immunity-gut microbiota

Abstract Early-life antibiotic exposure is strongly associated with increased risk of developing ulcerative colitis (UC) during adolescence. While probiotic interventions may confer protective effects by modulating the gut microbiota and immune system, the long-term efficacy of Saccharomyces cerevisiae (SC) and its cell wall component mannan-oligosaccharides (MOS) in this context remains unclear. To investigate whether SC, alone or combined with MOS, provides protective effects against dextran sulfate sodium (DSS)-induced colitis in adolescent mice with prior early-life antibiotic exposure, and to elucidate the underlying regulatory mechanisms via the "immune–gut microbiota" axis.Compared with antibiotic exposure alone, SC intervention reduced inflammatory scores in juvenile colitis, downregulated pro-inflammatory mediators such as IL-6 and TNF-α in the colon, and upregulated anti-inflammatory factors including IL-10. SC also partially restored antibiotic-induced reductions in gut microbial α-diversity and promoted enrichment of beneficial bacteria such as Akkermansia . Furthermore, SC increased fecal SCFA concentrations (e.g.acetate, butyrate) and enhanced intestinal secretory immunoglobulin A (sIgA) levels. Long-term combined SC and MOS supplementation demonstrated synergistic effects in promoting colonization of beneficial taxa (e.g. Parabacteroides ), maintaining SCFA homeostasis, and augmenting sIgA secretion. SC provides sustained protection against adolescent colitis by regulating antibiotic-induced immune dysregulation and gut dysbiosis. The addition of MOS further enhances this protective effect, supporting the potential of "probiotic–prebiotic" combination strategies for preventing antibiotic-associated intestinal sequelae.