Interplay between Genetic Disorders and Gut Microbial Community: Rubinstein-Taybi Syndrome as a Model

Rubinstein-Taybi syndrome (RSTS) is a genetic disease affecting 1 out of 125,000 newborns characterized by intellectual disability, skeletal abnormalit the genes CREBBP, encoding for CBP protein, or EP300, encoding for p300 protein. As CBP and p300 are lysine acetyl-transferases, RSTS patients sho Pharmacological therapy with histone deacetylase inhibitors (HDACi) was shown to attenuate chromatin impairment improving the clinical phenotype in chain fatty acids, especially butyrate, display HDACi activity, the aim of this study was to assess the endogenous level of butyrate and the relative abu enrolled 23 RSTS patients and 16 healthy siblings (HC), as control group to minimize environmental factors having a well-recognized role on gut mic generation sequencing using V3-V4 hypervariable 16S rRNA genomic region. Fecal SCFAs were quantified by gas chromatography. Exogenous HDACi derived from RSTS patients was assessed by Alpha LISA technology. The biodiversity of gut communities (alpha-diversity) was similar for all the assesse difference among HC and RSTS subjects was highlighted in beta-diversity analyses, as Both unweighted and weighted Unifrac distances revealed a signi respectively). We found several significant differences in taxa relative abundance among the two groups across all phylogenetic levels. In particular, R Faecalibacterium and Roseburia. Fecal SCFA concentrations were similar except for butyrate that was found reduced in RSTS (p=0.07). LCLs treated acetylation compared to untreated cells.Despite sharing diet habits and the environment, RSTS gut microbiota is depleted in major butyrate-produc Deepening our knowledge of RSTS gut microbiota alterations could offer new hints to explore strategies aimed at restoring a normal microbial comm associated with RSTS, such as gastrointestinal discomfort.