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Bespoke plant glycoconjugates for gut microbiota-mediated drug targeting Ma, Wei Jen; Wang, Changqing; Kothandapani, Jagatheeswaran; Luzentales-Simpson, Matthew; Menzies, Susan; Bescucci, Danisa; Lange, Máximo; Fraser, Alexander; Gusse, Jenny; House, Kathaleen; Moote, Paul; Xing, Xiaohui; Grondin, Julie; Hui, Benjamin Wei Qiang; Clarke, Sandra; Shelton, Tara; Haskey, Natasha; Gibson, Deanna; Martens, Eric; Abbott, Wade; Inglis, G. Douglas; Sly, Laura; Brumer, Harry

Description

Abstract

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.

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Title	Bespoke plant glycoconjugates for gut microbiota-mediated drug targeting
Creator	Ma, Wei Jen; Wang, Changqing; Kothandapani, Jagatheeswaran; Luzentales-Simpson, Matthew; Menzies, Susan; Bescucci, Danisa; Lange, Máximo; Fraser, Alexander; Gusse, Jenny; House, Kathaleen; Moote, Paul; Xing, Xiaohui; Grondin, Julie; Hui, Benjamin Wei Qiang; Clarke, Sandra; Shelton, Tara; Haskey, Natasha; Gibson, Deanna; Martens, Eric; Abbott, Wade; Inglis, G. Douglas; Sly, Laura; Brumer, Harry
Date Issued	2025-03-13
Description	Abstract 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.
Subject	Other; Chemistry; Biochemistry; Microbiome; Inflammatory bowel disease; Mouse models; Immunology; Drug delivery; Steroids; Salicylates; Bioinformatics; Enzymology; Carbohydrates; Polysaccharides; Microbiology; NMR spectroscopy; Pharmacokinetics; Enzyme kinetics; Metagenomics; Gut bacteria; Histology; gross pathology; Cytokines
Type	Dataset
Notes	Dryad version number: 5 Version status: submitted Dryad curation status: Published Sharing link: http://datadryad.org/dataset/doi:10.5061/dryad.np5hqc04q</p> Storage size: 899833585 Visibility: public
Date Available	2025-03-07
Provider	University of British Columbia Library
License	CC0 1.0
DOI	10.14288/1.0448204
URI	https://doi.org/10.5683/SP3/OL6HI2
Publisher DOI	https://doi.org/10.5683/SP3/OL6HI2; https://doi.org/10.5061/dryad.np5hqc04q
Grant Funding Agency	Innovation, Science and Economic Development Canada; Canadian Institutes of Health Research; Canadian Institutes of Health Research; Natural Sciences and Engineering Research Council; Natural Sciences and Engineering Research Council; Natural Sciences and Engineering Research Council; Natural Sciences and Engineering Research Council; Agriculture and Agri-Food Canada; Michael Smith Health Research BC; Alberta Innovates; Crohn's and Colitis Canada; Crohn's and Colitis Canada; Crohn's and Colitis Canada; Michael Smith Health Research BC
Rights URI	http://creativecommons.org/publicdomain/zero/1.0
Aggregated Source Repository	Dataverse

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