β-Glucan-rich Hericium erinaceus hot-water extract ameliorates acute colitis by suppressing inflammation, preserving the epithelial barrier, and modulating gut microbiota ecosystem.

Inflammatory bowel disease (IBD) is a chronic disorder marked by mucosal barrier disruption, immune imbalance, and gut dysbiosis. Polysaccharide-enriched extracts of Hericium erinaceus (HE) have shown anti-colitic effects, but the role of its β-glucan-rich water extract (HE-HW) remains unclear. By investigating a commercially relevant β-glucan-rich extract rather than isolated polysaccharides, this work addresses a key translational gap in HE research. HE-HW, rich in 1,3:1,6-β-glucan (286.4 mg/g), was evaluated using cells and mouse colitis models. In RAW 264.7 macrophages, HE-HW (1-10 μg/mL) suppressed lipopolysaccharide-induced nitric oxide and pro-inflammatory cytokines (IL-6, MCP-1) without cytotoxicity. In DSS-stimulated Caco-2 cells, HE-HW downregulated inflammatory mediators and restored tight junction genes (occludin, ZO-1, MUC2). In DSS-induced colitis mice, oral HE-HW (1 or 5 mg/kg/day) improved disease activity and colon length while normalizing serum and tissue cytokines and immunoglobulins. Histology confirmed reduced mucosal damage, muscle thickening, and collagen accumulation. Microbiome profiling showed HE-HW attenuated DSS-associated enrichment of Erysipelatoclostridium, Faecalibaculum, and Olsenella, suggesting selective remodeling of inflammation-related microbial populations. These findings demonstrate that β-glucan-rich HE-HW protects against colitis by modulating inflammation, reinforcing epithelial integrity, and rebalancing gut microbiota.