Gut microbiome profiling of Rubinstein-Taybi syndrome patients

Rubinstein-Taybi syndrome (RSTS, OMIM #180849, #613684) is a rare autosomal-dominant disease characterized by intellectual disability, postnatal growth deficiency with excessive weight gain in adolescence, distinctive dysmorphisms, and skeletal abnormalities with a wide spectrum of multiple congenital anomalies. RSTS is caused by pathogenic variants in one of two highly conserved genes: CREBBP (16p13.3), coding for cAMP response element binding and EP300 (22q13.2), coding for E1A-associated protein p300, both belonging to the lysine acetyl transferases family, acting as co-factors of transcription, and required in multiple pathways of cell growth control, DNA repair, cell differentiation, and tumor suppression. Preliminary studies supported the hypothesis that RSTS is caused by acetylation imbalance and that a key component can be represented by the role of gut microbiota (i.e. commensal microbial community) in protein acetylation. Among short chain fatty acids , endogenous butyrate is exclusively produced by commensal microorganisms and is the most potent histone deacetylase inhibitor among natural compounds. Indeed, besides SCFAs production, an altered gut microbiota could participate in the typical RSTS growth trend (weight deficit in infancy and excessive weight gain after puberty) and to comorbidities often associated to RSTS, such as gastrointestinal discomfort. We enrolled 23 RSTS subjects and 16 healthy siblings, as a control group and performed microbiota profiling by V3-V4 16S rRNA gene-targeted sequencing.