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>

<b>摘要</b><br/><p>哺乳动物肠道菌群具有独特的代谢通路，其治疗潜力尚未被充分挖掘。基于对人类肠道菌群代谢膳食纤维的分子机制的深入理解，我们设计了一种靶向药物递送系统，该系统基于一种名为GlycoCaging的复杂植物寡糖的定制糖缀合物。将GlycoCaging技术应用于示例性抗炎药物，可通过土著肠道细菌特有的糖苷酶（glycosidases）触发活性分子的释放。在炎症性肠病的小鼠模型中，GlycoCaging技术增强了药物疗效，并消除了脱靶效应。对个体人类肠道菌群的生化和宏基因组分析证实了该策略的广泛适用性。</p>