Preliminary Investigation of Microbiome and Dietary Differences in Patients with Phenylketonuria on Enzyme Substitution Therapy Compared to Traditional Therapies.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism that impairs the function of the enzyme phenylalanine hydroxylase. 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 with those receiving the enzyme substitution therapy Palynziq on a liberalized diet while controlling blood Phe levels to <600 µmol/L (to convert to mg/dL divide by 60.5). 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 6 patients on Palynziq eating a liberalized diet without medical food intake for more than 3 years were selected from the University of Kentucky Metabolic Clinic from August to December 2019. MAIN OUTCOME MEASURES: Nutrient intake from 3-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 patients receiving Palynziq 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 < .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 < .05). Pathway analysis depicted greater enrichment in carotenoid and amino acid metabolism pathways in the Traditional group (P < .05). Protein (% kcal), dietary fiber (g), fat (% kcal), linolenic acid (% Dietary Reference Intakes), 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 with those treated with traditional Phe-restricted diets. Several of these dietary differences may affect the microbiome architecture.

A review of the effects of nuts on appetite, food intake, metabolism, and body weight.

Tree nuts and peanuts are good sources of many nutrients and antioxidants, but they are also energy dense. The latter often limits intake because of concerns about their possible contribution to positive energy balance. However, evidence to date suggests that nuts are not associated with predicted weight gain. This is largely due to their high satiety value, leading to strong compensatory dietary responses, inefficiency in absorption of the energy they contain, a possible increment in resting energy expenditure, and an augmentation of fat oxidation. Preliminary evidence suggests that these properties are especially evident when they are consumed as snacks.