Oral Mycobiome Alterations in Children with Phenylketonuria: Associations with Dietary Intake and Metabolic Context-A...

Phenylketonuria (PKU) is a metabolic disorder requiring a strict low-phenylalanine diet. Oral health impairment, including bacteriome dysbiosis, is common in PKU, yet the mycobiome remains poorly defined. This pilot study aimed to characterise the salivary oral mycobiome of children with PKU compared with controls and to explore associations with dietary intake.

Saliva samples from 18 children, including 8 patients with PKU and 10 age-matched controls, were profiled using internal transcribed spacer (ITS) amplicon sequencing. Alpha/beta diversity, taxonomic composition, diet-fungi correlations, discriminative taxa and LEfSe were analysed.

Alpha diversity did not differ significantly between groups after correction for multiple comparisons, although exploratory subgroup analyses suggested lower evenness in PKU children aged <10 years compared with older controls. Beta diversity differed by diagnosis (PERMANOVA: F = 1.7251, p = 0.0062) and in the age-diagnosis model (F = 1.8502, p = 0.0004). Taxonomic analyses identified nominal differences in several fungal taxa, including Candida (p = 0.011), Saccharomycetales_fam_Incertae_sedis (p = 0.011), Naganishia (p = 0.020), and Aspergillaceae (p = 0.036) in PKU samples; however, these findings should be interpreted as exploratory because many did not remain significant after FDR correction. Diet-mycobiome analyses identified selected FDR-supported associations, including an inverse relationship between phenylalanine intake and Naganishia in PKU.

This pilot study suggests preliminary compositional differences in the oral mycobiome of children with PKU that may be related to dietary therapy and metabolic context. These exploratory findings require validation in larger cohorts with detailed oral health assessment and control of confounders.