Comparison of Gut Microbial Community in Infants and Toddlers with and without Phenylketonuria

Thesis (Master's)--University of Washington, 2014University of Washington Abstract Gut Microbial Community in Infants and Toddlers with and without Phenylketonuria (PKU) Melissa Jane Edwards Chair of the Supervisory Committee: Professor Johanna W. Lampe Nutrition Background: Prebiotics are non-digestible food components that selectively stimulate the growth and/or activity of beneficial bacteria in the colon and contribute to improved human health. Infants and young children with inborn errors of metabolism (IEM), such as phenylketonuria (PKU) consume low amounts of dietary sources of prebiotics because of their comprehensive dietary restriction of phenylalanine-containing foods. It is unknown if the amount of prebiotics that patients with PKU consume provides adequate substrate to support a beneficial gut microbial community (GMC). The GMC is involved in many aspects of human health, including providing a barrier for colonization of pathogens, contributing to energy salvage and regulation, and modulating immune function. Methods: We conducted an observational pilot study to characterize the GMC profiles of 6 patients with PKU and compare them to those of 13 age- and sex-matched controls. Study activities included (1) administration of a brief questionnaire to collect data about general health status, use of antibiotics, mode of infant delivery, gestational age at birth, birth weight, maternal diet and maternal pre- and probiotic use; (2) analysis of 3-day food records for nutrient and pre-biotic intake; and (3) assessment of GMC using bacterial DNA extracted from fecal samples. Results: The questionnaire revealed no statistically significant differences between the two groups. The analysis of the 3-day food record revealed significant differences in protein, phenylalanine and dietary fiber intakes. There was an inadequate number of patients receiving breast milk or standard infant formula to compare prebiotic intake between the two groups. The assessment of GMC revealed bacteria were distributed across 5 phyla: Firmicutes (57%), Bacteroidetes (37%), Proteobacteria (2.3%), Verrucomicrobia (0.4%), and Actinobacteria (2.7%). There was no significant difference in the distribution of bacterial phyla between control and PKU subjects. There was no statistically significant difference in the Shannon diversity index, which is a measure of the evenness and richness of the GMC within a person, between controls and participants without PKU (p=0.16). Although not statistically significant, diversity tended to be lower in the children with PKU compared to controls. Conclusion: This pilot study provided important initial insight into the GMC differences between patients with PKU and children receiving usual dietary care and generated important preliminary data needed for design of a larger, comprehensive study. Given that establishment of a healthy, diverse GMC may have implications for the long-term health of individuals, the ultimate goal of this study was to inform the development of optimized nutritional products that may improve the lives of individuals with PKU