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Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome
The short-chain fatty acid butyrate, produced by the gut microbiota, acts as a potent histone deacetylase (HDAC) inhibitor. We assessed possible ameliorative effects of butyrate, relative to other HDAC inhibitors, in in vitro and in vivo models of Rubinstein–Taybi syndrome (RSTS), a severe neurodeve...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037970/ https://www.ncbi.nlm.nih.gov/pubmed/33807238 http://dx.doi.org/10.3390/ijms22073621 |
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author | Di Fede, Elisabetta Ottaviano, Emerenziana Grazioli, Paolo Ceccarani, Camilla Galeone, Antonio Parodi, Chiara Colombo, Elisa Adele Bassanini, Giulia Fazio, Grazia Severgnini, Marco Milani, Donatella Verduci, Elvira Vaccari, Thomas Massa, Valentina Borghi, Elisa Gervasini, Cristina |
author_facet | Di Fede, Elisabetta Ottaviano, Emerenziana Grazioli, Paolo Ceccarani, Camilla Galeone, Antonio Parodi, Chiara Colombo, Elisa Adele Bassanini, Giulia Fazio, Grazia Severgnini, Marco Milani, Donatella Verduci, Elvira Vaccari, Thomas Massa, Valentina Borghi, Elisa Gervasini, Cristina |
author_sort | Di Fede, Elisabetta |
collection | PubMed |
description | The short-chain fatty acid butyrate, produced by the gut microbiota, acts as a potent histone deacetylase (HDAC) inhibitor. We assessed possible ameliorative effects of butyrate, relative to other HDAC inhibitors, in in vitro and in vivo models of Rubinstein–Taybi syndrome (RSTS), a severe neurodevelopmental disorder caused by variants in the genes encoding the histone acetyltransferases CBP and p300. In RSTS cell lines, butyrate led to the patient-specific rescue of acetylation defects at subtoxic concentrations. Remarkably, we observed that the commensal gut microbiota composition in a cohort of RSTS patients is significantly depleted in butyrate-producing bacteria compared to healthy siblings. We demonstrate that the effects of butyrate and the differences in microbiota composition are conserved in a Drosophila melanogaster mutant for CBP, enabling future dissection of the gut–host interactions in an in vivo RSTS model. This study sheds light on microbiota composition in a chromatinopathy, paving the way for novel therapeutic interventions. |
format | Online Article Text |
id | pubmed-8037970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80379702021-04-12 Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome Di Fede, Elisabetta Ottaviano, Emerenziana Grazioli, Paolo Ceccarani, Camilla Galeone, Antonio Parodi, Chiara Colombo, Elisa Adele Bassanini, Giulia Fazio, Grazia Severgnini, Marco Milani, Donatella Verduci, Elvira Vaccari, Thomas Massa, Valentina Borghi, Elisa Gervasini, Cristina Int J Mol Sci Article The short-chain fatty acid butyrate, produced by the gut microbiota, acts as a potent histone deacetylase (HDAC) inhibitor. We assessed possible ameliorative effects of butyrate, relative to other HDAC inhibitors, in in vitro and in vivo models of Rubinstein–Taybi syndrome (RSTS), a severe neurodevelopmental disorder caused by variants in the genes encoding the histone acetyltransferases CBP and p300. In RSTS cell lines, butyrate led to the patient-specific rescue of acetylation defects at subtoxic concentrations. Remarkably, we observed that the commensal gut microbiota composition in a cohort of RSTS patients is significantly depleted in butyrate-producing bacteria compared to healthy siblings. We demonstrate that the effects of butyrate and the differences in microbiota composition are conserved in a Drosophila melanogaster mutant for CBP, enabling future dissection of the gut–host interactions in an in vivo RSTS model. This study sheds light on microbiota composition in a chromatinopathy, paving the way for novel therapeutic interventions. MDPI 2021-03-31 /pmc/articles/PMC8037970/ /pubmed/33807238 http://dx.doi.org/10.3390/ijms22073621 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Di Fede, Elisabetta Ottaviano, Emerenziana Grazioli, Paolo Ceccarani, Camilla Galeone, Antonio Parodi, Chiara Colombo, Elisa Adele Bassanini, Giulia Fazio, Grazia Severgnini, Marco Milani, Donatella Verduci, Elvira Vaccari, Thomas Massa, Valentina Borghi, Elisa Gervasini, Cristina Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome |
title | Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome |
title_full | Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome |
title_fullStr | Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome |
title_full_unstemmed | Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome |
title_short | Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome |
title_sort | insights into the role of the microbiota and of short-chain fatty acids in rubinstein–taybi syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037970/ https://www.ncbi.nlm.nih.gov/pubmed/33807238 http://dx.doi.org/10.3390/ijms22073621 |
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