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

TL;DR

This study explores how the gut fungal community differs in children with phenylketonuria (PKU) compared to healthy children, and how these differences may relate to diet and age.

Contribution

The study is the first to investigate the gut mycobiome in PKU patients, revealing age-dependent fungal shifts linked to dietary restrictions.

Findings

PKU patients showed increased abundance of Eurotiales and Aspergillaceae fungi compared to controls.

Geotrichum fungal abundance correlated with higher protein and phenylalanine intake in PKU patients.

Dietary treatment in PKU is associated with age-dependent shifts in gut fungal composition.

Abstract

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, p = 0.09; ANOVA: p = 0.0609). PKU patients showed increased Eurotiales (p = 0.029), Aspergillaceae (p = 0.029), and Penicillium (p = 0.11) and decreased Physalacriaceae (0% vs. 5.84% in controls) and Malassezia (p = 0.13). Spearman’s analysis showed significant correlations between Geotrichum and intake of protein (ρ = 0.55, p = 0.0127) and phenylalanine (ρ = 0.70, p = 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, Aspergillaceae, and Penicillium, involved in carbohydrate/lipid metabolism and mucosal inflammation. These findings highlight the potential of gut fungi as nutritional and clinical biomarkers in PKU.

Figures