Bespoke plant glycoconjugates for gut microbiota-mediated drug targeting

• 成果类型: Article
• 署名作者: Ma, Wei Jen; Wang, Changqing; Kothandapani, Jagatheeswaran; Luzentales-Simpson, Matthew; Menzies, Susan C.; Bescucci, Danisa M.; Lange, Maximo E.; Fraser, Alexander S. C.; Gusse, Jenny F.; House, Kathaleen E.; Moote, Paul E.; Xing, Xiaohui; Grondin, Julie M.; Hui, Benjamin Wei-Qiang; Clarke, Sandra T.; Shelton, Tara G.; Haskey, Natasha; Gibson, Deanna L.; Martens, Eric C.; Abbott, D. Wade; Inglis, G. Douglas; Sly, Laura M.; Brumer, Harry
• 署名单位: University of British Columbia; University of British Columbia; BC Children's Hospital; University of British Columbia; University of British Columbia; Agriculture & Agri Food Canada; University of British Columbia; University of British Columbia Okanagan; University of Michigan System; University of Michigan
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12587
• DOI: 10.1126/science.adk7633
• 发表日期: 2025-06-26
• 页码: 1410-1416
• 关键词: scid mice; ship; dexamethasone; glucuronide; expression; disease

摘要

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.