Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing.

Submitted by Nuzia Santos ([email protected]) on 2017-04-12T19:01:34Z No. of bitstreams: 1 ve_Oliveira_Felipe_Phenylketonuria_CPqRR_2016.pdf: 5478745 bytes, checksum: 1d0d9580be46c56f2b8a9c16a83097e5 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2017-04-12T19:10:17Z (GMT) No. of bitstreams: 1 ve_Oliveira_Felipe_Phenylketonuria_CPqRR_2016.pdf: 5478745 bytes, checksum: 1d0d9580be46c56f2b8a9c16a83097e5 (MD5)Made available in DSpace on 2017-04-12T19:10:17Z (GMT). No. of bitstreams: 1 ve_Oliveira_Felipe_Phenylketonuria_CPqRR_2016.pdf: 5478745 bytes, checksum: 1d0d9580be46c56f2b8a9c16a83097e5 (MD5) Previous issue date: 2016Universidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brazil/Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório Basic Research and Advanced Investigations in Neurosciences. Porto Alegre, RS, BrazilUniversidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brazil/Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório Basic Research and Advanced Investigations in Neurosciences. Porto Alegre, RS, BrazilUniversidade Federal do Pampa. Centro Interdisciplinar de Pesquisas em Biotecnologia–CIP-Biotec. São Gabriel, RS, BrazilUniversity of Florida. Emerging Pathogens Institute. College of Public Health and Health Professions and College of Medicine. Department of Epidemiology. Gainesville, FL, United States of AmericaOswaldo Cruz Fundation. René Rachou Research Centre. Genomics and Computational Biology Group. Belo Horizonte, MG, BrazilUniversity of Florida. Emerging Pathogens Institute. College of Public Health and Health Professions and College of Medicine. Department of Epidemiology. Gainesville, FL, United States of AmericaHospital de Clínicas de Porto Alegre. Serviço de Genética Médica. Porto Alegre, RS, BrazilHospital de Clínicas de Porto Alegre. Serviço de Genética Médica. Porto Alegre, RS, BrazilUniversidade Federal do Pampa. Centro Interdisciplinar de Pesquisas em Biotecnologia–CIP-Biotec. São Gabriel, RS, BrazilUniversidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brazil/Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório de Pesquisas Básicas e Aplicadas em Neurociencias. Porto Alegre, RS, BrazilPhenylketonuria (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

Bacterial phylotypes that differed between controls and patients with phenylketonuria, based on White’s non-parametric <i>t</i>-test.

<p>Bacterial phylotypes that differed between controls and patients with phenylketonuria, based on White’s non-parametric <i>t</i>-test.</p

Frequencies of most abundant phyla (>1% of group sequences) in the phenylketonuria (n = 8) and control (n = 10) groups.

<p>*<i>p</i>-value < 0.05. Top panel represents the average abundance per treatment. Bottom panel represents the average of phyla per patient.</p

Alpha diversity measurements of microbial communities in the phenylketonuria and control groups.

<p>Each panel represent one alpha diversity measure as follow: Observed = total number of OTU’s observed; Chao1 and ACE = richness estimators (estimate the total number of OTU’s present in a community); Shannon, Simpson and InvSimpson = microbial indexes of diversity. Boxes span the first to third quartiles; the horizontal line inside the boxes represents the median. Whiskers extending vertically from the boxes indicate variability outside the upper and lower quartiles, and the single black circles indicate outliers.</p

Comparison of phenylketonuria and control groups.

<p>Comparison of phenylketonuria and control groups.</p