Synergistic mechanism of mannan-Bacteroides-Akkermansia muciniphila axis: a new paradigm for treating ulcerative colitis by targeting bacterial metabolic

In recent years, the rapidly rising incidence of ulcerative colitis (UC) has imposed a substantial burden on patients and society. Current therapeutic options remain limited, necessitating novel interventions. Dietary fiber supplementation and microbiota modulation represent promising therapeutic strategies. In UC patients and a dextran sulfate sodium (DSS)-induced murine UC model, we observed a significant reduction in the abundance of Akkermansia muciniphila (AKK). Mannan intervention markedly alleviated UC symptoms and restored AKK abundance, leading us to hypothesize that mannan exerts therapeutic effects by promoting AKK proliferation. However, in vitro co-culture experiments revealed that AKK cannot directly utilize mannan, whereas Bacteroides species efficiently metabolized mannan. Enriched Bacteroides further converted primary bile acids into secondary bile acids (e.g., deoxycholic acid, DCA), which subsequently stimulated AKK growth. Animal experiments demonstrated that the expanded AKK population enhanced intestinal mucosal protection and reduced proinflammatory cytokine levels, ultimately ameliorating UC. These findings propose a novel prebiotic-based therapeutic strategy—mannan-Bacteroides-AKK axis—for UC management, highlighting a synergistic microbial cascade mechanism. This work establishes a pioneering paradigm for the pharmacological utilization of polysaccharides in microbiota-targeted therapies.