Bespoke plant glycoconjugates for gut microbiota–mediated drug targeting
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.
Authors
- Benjamin Wei‐Qiang Hui
- Tara Shelton
- Paul E. Moote (ORCID: https://orcid.org/0009-0007-4359-4872)
- D. Wade Abbott (ORCID: https://orcid.org/0000-0003-4893-5799)
- G. Douglas Inglis (ORCID: https://orcid.org/0000-0003-1769-7863)
- Matthew Luzentales-Simpson (ORCID: https://orcid.org/0000-0001-8034-5217)
- Changlin Wang (ORCID: https://orcid.org/0009-0009-4052-5737)
- Danisa M. Bescucci
- Jagatheeswaran Kothandapani (ORCID: https://orcid.org/0000-0001-9235-6079)
- Jenny F. Gusse
- Xiaohui Xing (ORCID: https://orcid.org/0000-0002-9129-6542)
- Deanna L. Gibson (ORCID: https://orcid.org/0000-0003-0052-7550)
- M Lange (ORCID: https://orcid.org/0009-0005-6028-4492)
- Susan C. Menzies
- Julie M. Grondin (ORCID: https://orcid.org/0000-0002-3004-5715)
- Eric C. Martens (ORCID: https://orcid.org/0000-0001-6681-2990)
- Natasha Haskey (ORCID: https://orcid.org/0000-0001-7349-9445)
- Kathaleen E. House
- Laura M. Sly (ORCID: https://orcid.org/0000-0002-1673-467X)
- Sandra T. Clarke (ORCID: https://orcid.org/0000-0003-0919-5652)
- Harry Brumer (ORCID: https://orcid.org/0000-0002-0101-862X)
- Alexander S. C. Fraser (ORCID: https://orcid.org/0009-0003-2253-7706)
- Wei Jen (ORCID: https://orcid.org/0000-0002-9070-6263)
Institutions
- Agriculture and Agri-Food Canada (CA)
- University of Michigan (US)
- Canada's Michael Smith Genome Sciences Centre (CA)
- BC Children's Hospital (CA)
- Okanagan University College (CA)
Publication Details
- Journal
- Science
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1126/science.adk7633
- Citations
- 11
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 8.87