Bespoke plant glycoconjugates for gut microbiota-mediated drug targeting

<b>Abstract</b><br/><p>The gut microbiota of mammals possess unique 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 based on bespoke glycoconjugates of a complex plant oligosaccharide called GlycoCaging. GlycoCaging of exemplar anti-inflammatory drugs enabled the release of active molecules triggered by unique glycosidases of autochthonous gut bacteria. GlycoCaging ensured 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.</p>