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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| Published in: | Journal of medicinal chemistry Vol. 64; no. 23; p. 17277 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
09.12.2021
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| ISSN: | 1520-4804, 1520-4804 |
| Online Access: | Get more information |
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| Abstract | 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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| AbstractList | 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 ex vivo 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.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 ex vivo 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. 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. |
| Author | Brigidi, Patrizia Falchi, Federico Barone, Monica Turroni, Silvia Rampelli, Simone Armirotti, Andrea Cavalli, Andrea Candela, Marco Biagi, Elena Bertozzi, Sine Mandrup |
| Author_xml | – sequence: 1 givenname: Monica orcidid: 0000-0001-5229-570X surname: Barone fullname: Barone, Monica organization: Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, Bologna40138, Italy – sequence: 2 givenname: Simone surname: Rampelli fullname: Rampelli, Simone organization: Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, Bologna40126, Italy – sequence: 3 givenname: Elena surname: Biagi fullname: Biagi, Elena organization: Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, Bologna40126, Italy – sequence: 4 givenname: Sine Mandrup surname: Bertozzi fullname: Bertozzi, Sine Mandrup organization: Analytical Chemistry Lab, Istituto Italiano di Tecnologia, Via Morego 30, Genova16163, Italy – sequence: 5 givenname: Federico surname: Falchi fullname: Falchi, Federico organization: Molecular Horizon, Via Montelino 30, Bettona (PG)06084, Italy – sequence: 6 givenname: Andrea orcidid: 0000-0002-6370-1176 surname: Cavalli fullname: Cavalli, Andrea organization: Computational & Chemical Biology, Istituto Italiano di Tecnologia, Via Morego 30, Genova16163, Italy – sequence: 7 givenname: Andrea orcidid: 0000-0002-3766-8755 surname: Armirotti fullname: Armirotti, Andrea organization: Analytical Chemistry Lab, Istituto Italiano di Tecnologia, Via Morego 30, Genova16163, Italy – sequence: 8 givenname: Patrizia surname: Brigidi fullname: Brigidi, Patrizia organization: Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, Bologna40138, Italy – sequence: 9 givenname: Silvia surname: Turroni fullname: Turroni, Silvia organization: Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, Bologna40126, Italy – sequence: 10 givenname: Marco orcidid: 0000-0001-7420-790X surname: Candela fullname: Candela, Marco organization: Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, Bologna40126, Italy |
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| Title | Searching for New Microbiome-Targeted Therapeutics through a Drug Repurposing Approach |
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