Bespoke plant glycoconjugates for gut microbiota–mediated drug targeting

The gut microbiota of mammals possess distinctive metabolic pathways with untapped therapeutic potential. Using molecular insights into dietary fiber metabolism by the human gut microbiota, we designed a targeted drug delivery system, called GlycoCaging, that is based on bespoke glycoconjugates of a complex plant oligosaccharide. GlycoCaging of exemplar anti-inflammatory drugs enabled release of active molecules triggered by specific glycosidases of autochthonous gut bacteria. GlycoCaging ensured that drug efficacy was potentiated, and off-target effects were eliminated in murine models of inflammatory bowel disease. Biochemical and metagenomic analyses of gut microbiota of individual humans confirmed the broad applicability of this strategy.