The Prebiotic 2'-Fucosyllactose Ameliorates Colitis via an Akkermansia muciniphila-Mediated Prebiotic-Microbiota-Metabolite Axis.

Recent studies indicate that 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, alleviates inflammatory bowel disease (IBD) by modulating the gut microbiota, yet the underlying mechanisms and key functional bacteria involved remain unclear. This study employed fecal microbiota transplantation and an antibiotic-treated mouse model to investigate the role of 2'-FL-mediated gut microbiota in lipopolysaccharide-induced colitis, with a focus on Akkermansia muciniphila (A. muciniphila). Results demonstrated that 2'-FL intervention significantly enriched A. muciniphila in the gut and promoted the production of short-chain fatty acids (SCFAs). Fecal microbiota transplantation experiments confirmed that 2'-FL-modulated microbiota reshaped the gut ecosystem in recipient mice. Notably, monocolonization with A. muciniphila alone alleviated colitis, while coadministration of 2'-FL synergistically enhanced anti-inflammatory effects and SCFAs production. These findings reveal that 2'-FL operates via a "prebiotic-key bacterium-metabolite" axis, wherein A. muciniphila acts as a mediator to metabolize 2'-FL into SCFAs, orchestrating anti-inflammatory and barrier-protective responses.