Bespoke plant glycoconjugates for gut microbiota-mediated drug targeting
Data files
Mar 07, 2025 version files 899.83 MB
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CompoundNMR.7z
863.70 MB
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DecagingBacteriaHuman.zip
14.82 MB
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DecagingBacteriaMouse.zip
504.82 KB
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EnzymeKinetics.zip
1.53 MB
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Pharmacokinetics.zip
19.07 MB
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README.md
5.06 KB
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SHIPModel.zip
31.06 KB
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TCellTransferModel.zip
167.38 KB
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.
Description of the data and file structure
This dataset contains diverse data types and analyses, including from chemical synthesis, enzyme kinetics, murine models, pharmacokinetics, and metagenomics. Please see the published article for full experimental details, final data presentation, and interpretations.
Files are organized into compressed archives, first by overall analysis type, and then by corresponding figure in the published article.
File: CompoundNMR.7z
Contains original free-induction decay (FID) spectra and acquisition parameters for all one- and two-dimensional nuclear magnetic resonance (NMR) analyses of synthetic compounds. Within this archive, sub-archives contain data corresponding to Figures S16-S27, as indicated in the filenames: FigS16_FID_PerAcXXXX-OH.7z, FigS17_FID_PerAcXXXG-TCA.7z, FigS18_FID_PerAcXXXG-Dex.7z, FigS19-22_FID_XXXG-Dex.7z, FigS23-24_FID_XXXG-Bud.7z, FigS25-26_FID_XXXG5ASA.7z, FigS27_FID_AcXXXG-Carbonate.7z.
File: EnzymeKinetics.zip
Contains enzyme assay data and Michaelis-Menten analyses for GlycoCaged compounds corresponding to Figure 1E. Within this archive, sub-archives contain data for each compound and enzyme, as indicated in the filenames: Fig1E_XXXG-Dex.zip, Fig1E_XXXG-Pred.zip, Fig1E_XXXG-Bude.zip. Data processing spreadsheets (.xlsx) and graphing software files (.opj) are provided.
File: TCellTransferModel.zip
Contains all numerical gross pathology, histopathology, cytokine assay, and flow cytometry data for the T Cell Transfer mouse model, corresponding to Figures 2 and S8. Within this archive, spreadsheet files (.xlsx) are named by figure: Figure2_MouseData.xlsx, FigureS8_MouseData.xlsx. Within each file, data is organized into individual sheets by figure panel letter.
File: SHIPModel.zip
Contains all numerical gross pathology, histopathology, and cytokine assay data for the SHIP-/- mouse model, corresponding to Figures 3, 4, and S10. Within this archive, spreadsheet files (.xlsx) are named by figure: Figure3_MouseGIData.xlsx, Figure4_MouseLungData.xlsx, FigureS10_MouseWild-TypeData.xlsx. Within each file, data is organized into individual sheets by figure panel letter.
File: Pharmacokinetics.zip
Contains pharmacokinetic data obtained by LC-MS/MS corresponding to Figures S9 and S11. Within this archive, sub-archives contain data for each administered compound and biological sample, with filenames indicating the corresponding figure panel: FigureS9PanelA.zip through FigureS9PanelD.zip, FigureS11PanelA.zip through FigureS11PanelBB.zip. Within sub-archives, original report files from the MS service facility (.pdf or .xlsx), data processing spreadsheets (.xlsx), and graphing software files are provided (.opj).
File: DecagingBacteriaMouseGut.zip
Contains fluorimetric assay data and colony enumeration data regarding the presence of prodrug-decaging (xyloglucanase-positive) bacteria in the gastrointestinal tracts of mice. Subfolders within this archive contain data corresponding to Figures S5-S7, as indicated by the folder names. Individual filenames indicate corresponding figure panel and data type. Data processing spreadsheets (.csv, .xlsx), statistical analysis results (.pdf), and graphing software files are provided (.jnb).
File: DecagingBacteriaHumanGut.zip
Contains fluorimetric assay data, enumeration data, and metagenome analyses regarding the presence of prodrug-decaging (xyloglucanase-positive) bacteria in the gastrointestinal tracts of humans. Within this archive, sub-archives contain data corresponding to Figures 5, and S12-13, as indicated in the filenames: FigS12_HealthyHumanAssay.zip, Fig5AB_IBD+ControlsAssay.zip, Fig5CD+S13+S14_Metagenomics.zip. An additional README.md file describes in detail the file structure within the Metagenomics archive.
Access information
Publicly available metagenomes and associated metadata from the Human Microbiome Project 2 (HMP2) study were downloaded from the Human Microbiome Bioactives Resource data portal (https://portal.microbiome-bioactives.org/).
Code/software
- NMR data can be visualized with various software e.g., Bruker TopSpin, Mestrelab Mnova NMR (45-day free trial version currently available, March 2025). One-dimensional NMR data may be visualized with Mnova NMR Lite.
- Spreadsheets (.xlsx) and tabular data (.tsv) can be viewed with Microsoft Excel or equivalent.
- Graphical software data can be viewed with SigmaPlot (.jnb) or Origin (.opj). For Origin files, Origin Viewer is currently (March 2025) freely available.
- Scripts used to analyze metagenomic data are available on Zenodo and GitHub (DOI:10.5281/zenodo.14828870). Please see the Materials and Methods section of the published article for details on the analysis pipeline, including other publicly available software used.