The Gut Mycobiome and Nutritional Status in Paediatric Phenylketonuria: A Cross-Sectional Pilot Study.

BACKGROUND

Phenylketonuria (PKU) is a metabolic disorder managed through a strict, lifelong low-phenylalanine diet, which may influence gut microbiome dynamics. While gut bacterial alterations in PKU are increasingly investigated, the fungal community (mycobiome) remains largely unexplored. This study compared gut mycobiome composition and dietary profiles of paediatric PKU patients and healthy controls, stratified by age (<10 and 10-18 years).

METHODS

Stool samples from 20 children (10 PKU, 10 controls) were analysed using ITS1/ITS2 amplicon sequencing. Nutritional status was assessed using Body Mass Index percentiles (Polish standards), and nutrient intake was evaluated from three-day dietary records compared to national reference values. Correlations between fungal taxa and dietary factors were explored.

RESULTS

Although alpha diversity did not differ significantly, beta diversity and LEfSe analyses revealed distinct fungal profiles between PKU patients and controls, indicating a trend toward group separation (PERMANOVA: F = 1.54646, = 0.09; ANOVA: = 0.0609). PKU patients showed increased Eurotiales ( = 0.029), ( = 0.029), and ( = 0.11) and decreased (0% vs. 5.84% in controls) and ( = 0.13). Spearman's analysis showed significant correlations between and intake of protein ( = 0.55, = 0.0127) and phenylalanine ( = 0.70, = 0.0005).

CONCLUSIONS

Dietary treatment in PKU is associated with age-dependent shifts in the gut mycobiome, notably increasing the abundance of taxa such as Eurotiales, , and , involved in carbohydrate/lipid metabolism and mucosal inflammation. These findings highlight the potential of gut fungi as nutritional and clinical biomarkers in PKU.