Vancomycin-sensitive gut microbiota drives Dendrobium officinale polysaccharide’s degradation and its protective effects against colitis in mice

While Dendrobium officinale polysaccharide (DOP) shows promise in treating colitis, previous research only correlated changes in gut microbiota composition with DOP’s effects, without elucidating the specific mechanism by which gut microbiota mediates DOP’s bioactivities. This study addresses this crucial gap by demonstrating the essential role of vancomycin-sensitive gut bacteria in mediating the anti-colitis effects of DOP. Using targeted antibiotic perturbation, we found that vancomycin, but not neomycin, abolished both DOP degradation and its therapeutic effects in colitis mice. This loss of efficacy was attributed to the depletion of mannan endo-1,4-β-mannosidase (EC 3.2.1.78), the key enzyme for DOP catabolism. The expression of this enzyme was increased in DOP-treated microbiota, together with a stronger catalytic ability in DOP degradation. We further identified Bifidobacterium pseudolongum, a vancomycin-sensitive species, as a crucial contributor to DOP fermentation and its anti-colitis effects. This bacterium initiates DOP’s degradation by cleaving it into bioactive mannan oligosaccharides. In summary, this research reveals that the breakdown of DOP by mannan endo-1,4-β-mannosidase in vancomycin-sensitive B. pseudolongum plays a crucial role in its anti-colitis effects. This work advances the field by demonstrating that vancomycin-sensitive bacteria, such as B. pseudolongum, mediate DOP’s efficacy and establishing polysaccharide catabolism as critical for its therapeutic activity.