Gut microbiota in phenylketonuria (PKU) disorder

Phenylketonuria (PKU; OMIM 261,600) is an autosomal recessive disorder of Phenylalanine (Phe) metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene. Loss of PAH enzymatic activity results in an impairment of phenylalanine to tyrosine conversion, consequently increasing phenylalanine concentrations in blood (hyperphenylalaninemia) and fluids throughout the body and reaching toxic concentrations in the brain. Various combinations of mutations result in a full metabolic phenotypes ranging from mild hyperphenylalaninaemia (MHP) to classical phenylketonuria (PKU), the latter requiring dietary management. The PKU diet is mainly made up of low-protein natural foods (vegetables, fruits) and special low protein products, which are low protein variants of some foods such as bread, pasta and biscuits.The aim of our study was to compare gut microbiota biodiversity (via 16S rRNA hypervariable V3-V4 regions amplification and sequencing) in a dataset composed by 18 children with PKU, on low-Phe diet, and by 19 children with MHP, on unrestricted diet. The low phenylalanine diet might modify gut microbiota composition and affect gut homeostasis of PKU subjects.