Di Fede, E., Ottaviano, E., Grazioli, P., Ceccarani, C., Galeone, A., Parodi, C., Colombo, E.A., Bassanini, G., Fazio, G., Severgnini, M., Milani, D., Verduci, E., Vaccari, T., Massa, V., Borghi, E., Gervasini, C. (2021). Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein-Taybi Syndrome.  Int. J. Mol. Sci. 22(7): 3621.

FBrf0248597

Research paper

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.

PMC8037970 (PMC) (EuropePMC)