Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome

International Journal of Molecular Sciences

Thomas Vaccari¹  Antonio Galeone¹  Paolo Grazioli²  Valentina Massa²  Emerenziana Ottaviano²  Elvira Verduci²  Cristina Gervasini²  ElisaAdele Colombo²  Elisabetta Di Fede²  Elisa Borghi²  Chiara Parodi²  Giulia Bassanini²  Camilla Ceccarani²  Donatella Milani³  Marco Severgnini⁴  Grazia Fazio⁵ 

[1] Department of Biosciences, Università degli Studi di Milano, 20133 Milano, Italy;Department of Health Sciences, Università degli Studi di Milano, 20142 Milan, Italy;Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;Institute of Biomedical Technologies, Italian National Research Council, Segrate, 20054 Milan, Italy;Tettamanti Research Center, Department of Pediatrics, Università degli Studi di Milano-Bicocca, MBBM Foundation/San Gerardo Hospital, 20900 Monza, Italy;

关键词: Rubinstein–Taybi syndrome;    butyrate;    microbiota;    HDACi;    histones;   

DOI  :  10.3390/ijms22073621

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown