LAUSR

BACKGROUND Phenylketonuria (PKU) is an inborn error of metabolism that impairs the function of the enzyme phenylalanine hydroxylase (PAH). Historical treatment includes limiting dietary phenylalanine (Phe) consumption while supplementing with medical food; however, this treatment has been associated with complications, such as nutritional deficiencies and disruptions in the gut microbiota. OBJECTIVE The study aim was to compare dietary and gut microbiome differences between adult patients on a traditional PKU diet to those receiving the enzyme substitution therapy Palynziq on a liberalized diet while controlling blood Phe levels to <600 μmol/L. DESIGN A cross-sectional study was conducted comparing patients on a traditional Phe-restricted diet with patients receiving Palynziq eating a liberalized diet. PARTICIPANTS/SETTING Six patients eating a traditional Phe-restricted diet with medical food and six patients on Palynziq eating a liberalized diet without medical food intake for >3 years were selected from the University of Kentucky Metabolic Clinic August to December 2019. MAIN OUTCOME MEASURES Nutrient intake from three-day diet records and fecal microbiome taxonomic abundances were analyzed. STATISTICAL ANALYSIS Mann-Whitney U-tests were used for dietary data analysis. Differential abundance analysis for microbiome taxa and pathway data was done using DESeq2 analysis. RESULTS Dietary data showed Palynziq patients consumed a lower percent of kilocalories from total protein and lower amounts of most micronutrients but consumed greater amounts of intact protein and cholesterol (P<0.05). Microbiome data revealed a greater abundance of the phylum Verrucomicrobia and genus Lachnobacterium in the Traditional group and a greater abundance of the genus Prevotella in the Palynziq group (P<0.05). Pathway analysis depicted greater enrichment in carotenoid and amino acid metabolism pathways in the Traditional group (P<0.05). Protein (%kcal), dietary fiber (g), fat (%kcal), linolenic acid (%DRI), and age were correlated with the underlying microbial community structure for both groups combined. CONCLUSIONS Patients with PKU treated with Palynziq on a liberalized diet manifest significant differences in diet composition compared to those treated with traditional Phe-restricted diets. Several of these dietary differences may affect the microbiome architecture.