Bespoke plant glycoconjugates for gut microbiota–mediated drug targeting

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-05-01 DOI:10.1126/science.adk7633

Wei Jen Ma, Changqing Wang, Jagatheeswaran Kothandapani, Matthew Luzentales-Simpson, Susan C. Menzies, Danisa M. Bescucci, Máximo E. 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 L. Gibson, Eric C. Martens, D. Wade Abbott, G. Douglas Inglis, Laura M. Sly, Harry Brumer

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Abstract

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.

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定制植物糖缀合物用于肠道微生物介导的药物靶向

哺乳动物的肠道微生物群具有独特的代谢途径，具有未开发的治疗潜力。利用人类肠道微生物群对膳食纤维代谢的分子洞察力，我们设计了一种靶向药物递送系统，该系统基于一种复杂植物低聚糖的定制糖缀合物，称为GlycoCaging。典型抗炎药物的糖化能够释放由本地肠道细菌独特的糖苷酶触发的活性分子。在炎症性肠病小鼠模型中，糖介导确保了药物疗效的增强，并消除了脱靶效应。个体人类肠道微生物群的生化和宏基因组分析证实了这一策略的广泛适用性。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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