Insights into the role of the microbiota and of short-chain fatty acids in Rubinstein–Taybi syndrome
Articolo
Data di Pubblicazione:
2021
Citazione:
Insights into the role of the microbiota and of short-chain fatty acids in Rubinstein–Taybi syndrome / E. Di Fede, E. Ottaviano, P. Grazioli, C. Ceccarani, A. Galeone, C. Parodi, E.A. Colombo, G. Bassanini, G. Fazio, M. Severgnini, D. Milani, E. Verduci, T. Vaccari, V. Massa, E. Borghi, C. Gervasini. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:7(2021 Mar 31), pp. 3621.1-3621.16. [10.3390/ijms22073621]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
butyrate; HDACi; histones; microbiota; Rubinstein–Taybi syndrome
Elenco autori:
E. Di Fede, E. Ottaviano, P. Grazioli, C. Ceccarani, A. Galeone, C. Parodi, E.A. Colombo, G. Bassanini, G. Fazio, M. Severgnini, D. Milani, E. Verduci, T. Vaccari, V. Massa, E. Borghi, C. Gervasini
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