Fucose metabolism as a central axis linking inflammation, immunity, and cancer in the gut

Fucose metabolism and fucosylation are emerging as central regulators of intestinal epithelial integrity, immune homeostasis, host-microbiota interactions, and tumor progression. Increasing evidence implicates dysregulated fucosylation in the pathogenesis of inflammatory bowel disease (IBD), colorectal cancer (CRC), and necrotizing enterocolitis (NEC). Under physiological conditions, fucosylated glycans maintain mucus barrier stability, microbial symbiosis, and mucosal immune tolerance, whereas disrupted fucosylation promotes barrier dysfunction, dysbiosis, chronic inflammation, and intestinal carcinogenesis. In IBD, altered fucosylation impairs epithelial repair and immune regulation. In CRC, abnormal fucosylation drives oncogenic signaling, metabolic reprogramming, immune evasion, and metastasis while also providing clinically relevant biomarkers and therapeutic targets. In NEC, epithelial fucosylation and human milk oligosaccharides such as 2'-fucosyllactose protect against intestinal injury by enhancing epithelial regeneration, modulating inflammatory signaling, and regulating gut microbial composition. Collectively, these findings identify fucose metabolism linking epithelial biology, immunity, microbiota dynamics, and cancer progression in intestinal disease, highlighting fucosylation pathways as promising targets for diagnosis and therapy.