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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Podrobná bibliografia
Vydané v:	Journal of medicinal chemistry Ročník 64; číslo 23; s. 17277
Hlavní autori:	Barone, Monica, Rampelli, Simone, Biagi, Elena, Bertozzi, Sine Mandrup, Falchi, Federico, Cavalli, Andrea, Armirotti, Andrea, Brigidi, Patrizia, Turroni, Silvia, Candela, Marco
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 09.12.2021
Predmet:	Drug Repositioning Gastrointestinal Microbiome - drug effects Gene Expression Profiling High-Throughput Screening Assays Humans Validation Studies as Topic
ISSN:	1520-4804, 1520-4804
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1520-4804 1520-4804
DOI:	10.1021/acs.jmedchem.1c01333