β-Glucan Extracted from <i>Pichia kudriavzevii</i> DPUL-51–6Y, <i>Kluyveromyces marxianus</i> DPUL-F15, and <i>Saccharomyces cerevisiae</i> DPUL-C6 Shows Ameliorating Effects on DSS-Induced Ulcerative Colitis on BALB/c Mice

β-Glucans derived from yeast are recognized as beneficial food additives. This study evaluated crude β-glucan extracts from <i>Pichia kudriavzevii</i> DPUL-51-6Y, <i><i>Kluyveromyces marxianus</i></i> DPUL-F15, and <i><i>Saccharomyces cerevisiae</i></i> DPUL-C6 strains for their anticolitis potential. Chemical analysis revealed that β-glucan was the primary component (71.88-78.47% purity). Notably, the <i><i>S. cerevisiae</i></i> extract displayed superior thermal stability and hydration capacity. In RAW264.7 macrophages, β-glucan pretreatment at 100 μg/mL significantly reduced LPS-induced nitric oxide production and pro-inflammatory cytokines by suppressing NF-κB signaling through the reduction of p65 and IκB-α while simultaneously activating the Nrf2 and AHR pathways. In DSS-induced colitis BALB/c mice, oral administration of crude β-glucans alleviated intestinal damage by enhancing tight junction protein expression and restoring gut microbiota composition, characterized by an increased abundance of <i>Lactobacillus</i> and <i>Prevotella</i>. These effects were correlated with the increased production of microbial metabolites, including indole-3-lactic acid, indole-3-β-acrylic acid, tryptophol, and short-chain fatty acids (acetic, propionic, and butyric acids). Mechanistically, β-glucan mitigated colitis through the dual activation of Nrf2/AHR pathways and the inhibition of NF-κB. This study suggests that yeast-derived β-glucan plays a significant role in mitigating the inflammatory response and may alleviate ulcerative colitis by reshaping the microbial community and metabolite profiles in the host intestinal tract.