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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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