β-Glucan Extracted from Pichia kudriavzevii DPUL-51–6Y, Kluyveromyces marxianus DPUL-F15, and Saccharomyces cerevisiae 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 Pichia kudriavzevii DPUL-51–6Y, Kluyveromyces marxianus DPUL-F15, and Saccharomyces cerevisiae DPUL-C6 strains for their anticolitis potential. Chemical analysis revealed that β-glucan was the primary component (71.88–78.47% purity). Notably, the S. cerevisiae 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 Lactobacillus and Prevotella. 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.