title: Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing.
abstract: Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear.
authors.affiliation: Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Laboratório Basic Research and Advanced Investigations in Neurosciences (B.R.A.I.N)-Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Pinheiro de Oliveira
authors.affiliation: Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Laboratório Basic Research and Advanced Investigations in Neurosciences (B.R.A.I.N)-Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Roberta Hack
authors.initials: RH
authors.lastname: Mendes
authors.affiliation: Centro Interdisciplinar de Pesquisas em Biotecnologia-CIP-Biotec, Campus São Gabriel, Universidade Federal do Pampa, São Gabriel, Rio Grande do Sul, Brazil.
authors.forename: Priscila Thiago
authors.initials: PT
authors.lastname: Dobbler
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Volker
authors.initials: V
authors.lastname: Mai
authors.affiliation: Genomics and Computational Biology Group, René Rachou Research Centre-CPqRR, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Victor Salter
authors.initials: VS
authors.lastname: Pylro
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Sheldon G
authors.initials: SG
authors.lastname: Waugh
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Filippo
authors.initials: F
authors.lastname: Vairo
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Lilia Farret
authors.initials: LF
authors.lastname: Refosco
authors.affiliation: Centro Interdisciplinar de Pesquisas em Biotecnologia-CIP-Biotec, Campus São Gabriel, Universidade Federal do Pampa, São Gabriel, Rio Grande do Sul, Brazil.
authors.forename: Luiz Fernando Würdig
authors.identifier: http://orcid.org/0000-0003-1450-8828
authors.initials: LF
authors.lastname: Roesch
authors.affiliation: Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.|Laboratório Basic Research and Advanced Investigations in Neurosciences (B.R.A.I.N)-Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Ida Vanessa Doederlein
authors.initials: IV
authors.lastname: Schwartz
mesh_terms: D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004032:Diet; D005260:Female; D000069196:Gastrointestinal Microbiome; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D054892:Metagenome; D056186:Metagenomics / Q000379:methods; D010661:Phenylketonurias / Q000178:diet therapy* / Q000378:metabolism*; D012336:RNA, Ribosomal, 16S
chemical_list: D012336:RNA, Ribosomal, 16S