Quality of dietary carbohydrates affects gut microbial community of phenylketonuric subjects

Introduction - Low-phenylalanine diet, the cornerstone treatment for phenylketonuria (PKU), has been shown to increase glycemic index (GI) and glycemic load (GL), affecting the availability of substrates for microbial fermentation. Indeed, changes in the PKU gut microbiota and in microbial metabolites have been previously reported. Here we compared gut microbial communities of children with PKU and with mild hyperphenylalaninemia (MHP, unrestricted diet). Materials and Methods - Forty-two children (21 males/21 females, 4-18 years old) were enrolled in the study. We assessed dietary intake and performed gut microbiota analysis by next-generation sequencing using V3–V4 hypervariable 16S rRNA genomic region. Results - While alpha-diversity analysis revealed no significant differences between PKU and MHP groups, phylogenetic analysis highlighted a significant separation of gut microbiota according to both unweighted (p=0.008) and weighted Unifrac distances (p=0.03). Major differences were seen within the Firmicutes phylum. Indeed, PKU children were depleted in Faecalibacterium spp. and enriched in Blautia spp. and Clostridium spp. We found a divergent response of members of the Firmicutes phylum with respect of daily glycemic index, higher in PKU children. F. prausnitzii, unclassified Ruminococcaceae and, to a lesser extent Roseburia spp. negatively correlated with GI, whereas other Lachnospiraceae (unclassified) were positively associated. Indicator species analysis suggested Faecalibacterium prausnitzii to be related to MHP status, whereas Ruminococcus bromii to be associated to PKU. Discussion and Conclusions - Despite PKU children have a higher vegetables and fiber intakes, considered good substrates for beneficial microbes, the quality of carbohydrates ingested seems to particularly affect F. prausnitzii abundance, a biomarker for a healthy status. Indeed, F. prausnitzii is one of the key species for butyrate production. It still remains to evaluate whether an improvement of current free-amino acid formulas could rebalance the microbial community.