Bespoke plant glycoconjugates for gut microbiota–mediated drug targeting

作者：Wei Jen Ma, Changqing Wang, Jagatheeswaran Kothandapani, Matthew Luzentales-Simpson, Susan C. Menzies, Danisa M. Bescucci, M Lange, Alexander S. C. Fraser, Jenny F. Gusse, Kathaleen E. House, Paul E. Moote, Xiaohui Xing, Julie M. Grondin, Benjamin Wei‐Qiang Hui, Sandra T. Clarke, Tara G. Shelton, Natasha Haskey, Deanna Lynn Gibson, Eric C. Martens, D. Wade Abbott, G. Douglas Inglis, Laura M. Sly, Harry Brumer · 发表于：Science · 年份：2025 · DOI：10.1126/science.adk7633 · 被引用次数：30 · 研究领域：Gut microbiota and health、Clostridium difficile and Clostridium perfringens research

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.