Searching for New Microbiome-Targeted Therapeutics through a Drug Repurposing Approach

Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved molecules as next-generation microbiome therapeutics. Herein, we developed and validated an high-throughput screening platform─the mini g...

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Bibliographic Details
Published in:Journal of medicinal chemistry Vol. 64; no. 23; p. 17277
Main Authors: Barone, Monica, Rampelli, Simone, Biagi, Elena, Bertozzi, Sine Mandrup, Falchi, Federico, Cavalli, Andrea, Armirotti, Andrea, Brigidi, Patrizia, Turroni, Silvia, Candela, Marco
Format: Journal Article
Language:English
Published: United States 09.12.2021
Subjects:
Drug Repositioning
Gastrointestinal Microbiome - drug effects
Gene Expression Profiling
High-Throughput Screening Assays
Humans
Validation Studies as Topic
ISSN:1520-4804, 1520-4804
Online Access:Get more information
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Summary:Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved molecules as next-generation microbiome therapeutics. Herein, we developed and validated an high-throughput screening platform─the mini gut model─to underpin human gut microbiome response to molecular modulators. Ten FDA-approved compounds, selected based on maximum structural diversity of molecular fingerprints, were screened against the gut microbiome of five healthy subjects to characterize the ability of human-targeted drugs to modulate the human gut microbiome network. Three compounds, THIP hydrochloride, methenamine, and mesna, have shown promise as novel gut microbiome therapeutics in light of their capability of promoting health-associated features of the gut microbiome. Our findings provide a resource for future research on drug-microbiome interactions and lay the foundation for a new era of more precise gut microbiome modulation through drug repurposing, aimed at targeting specific dysbiotic events.
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ISSN:1520-4804
1520-4804
DOI:10.1021/acs.jmedchem.1c01333