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      Hepatic glycogen storage diseases are associated to microbial dysbiosis

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          Abstract

          Introduction

          The gut microbiome has been related to several features present in Glycogen Storage Diseases (GSD) patients including obesity, inflammatory bowel disease (IBD) and liver disease.

          Objectives

          The primary objective of this study was to investigate associations between GSD and the gut microbiota.

          Methods

          Twenty-four GSD patients on treatment with uncooked cornstarch (UCCS), and 16 healthy controls had their faecal microbiota evaluated through 16S rRNA gene sequencing. Patients and controls were ≥3 years of age and not on antibiotics. Faecal pH, calprotectin, mean daily nutrient intake and current medications were recorded and correlated with gut microbiome.

          Results

          Patients’ group presented higher intake of UCCS, higher prevalence of IBD (n = 04/24) and obesity/overweight (n = 18/24) compared to controls (n = 0 and 06/16, respectively). Both groups differed regarding diet (in patients, the calories’ source was mainly the UCSS, and the intake of fat, calcium, sodium, and vitamins was lower than in controls), use of angiotensin-converting enzyme inhibitors (patients = 11, controls = 0; p-value = 0.001) multivitamins (patients = 22, controls = 01; p-value = 0.001), and mean faecal pH (patients = 6.23; controls = 7.41; p = 0.001). The GSD microbiome was characterized by low diversity and distinct microbial structure. The operational taxonomic unit (OTU) abundance was significantly influenced by faecal pH (r = 0.77; p = 6.8e-09), total carbohydrate (r = -0.6; p = 4.8e-05) and sugar (r = 0.057; p = 0.00013) intakes.

          Conclusions

          GSD patients presented intestinal dysbiosis, showing low faecal microbial diversity in comparison with healthy controls. Those findings might be due to the disease per se, and/or to the different diets, use of UCSS and of medicines, and obesity rate found in patients. Although the main driver of these differences is unknown, this study might help to understand how the nutritional management affects GSD patients.

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          Most cited references21

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          Evidence-based clinical practice guidelines for inflammatory bowel disease

          Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn’s disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.
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            Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance

            This study aimed to determine if there is an association between dysbiosis and nonalcoholic fatty liver disease (NAFLD) independent of obesity and insulin resistance (IR). This is a prospective cross-sectional study assessing the intestinal microbiome (IM) of 39 adults with biopsy-proven NAFLD (15 simple steatosis [SS]; 24 nonalcoholic steatohepatitis [NASH]) and 28 healthy controls (HC). IM composition (llumina MiSeq Platform) in NAFLD patients compared to HC were identified by two statistical methods (Metastats, Wilcoxon). Selected taxa was validated using quantitative PCR (qPCR). Metabolites in feces and serum were also analyzed. In NAFLD, 8 operational taxonomic units, 6 genera, 6 families and 2 phyla (Bacteroidetes, Firmicutes) were less abundant and; 1 genus (Lactobacillus) and 1 family (Lactobacillaceae) were more abundant compared to HC. Lower abundance in both NASH and SS patients compared to HC were confirmed by qPCR for Ruminococcus, Faecalibacterium prausnitzii and Coprococcus. No difference was found between NASH and SS. This lower abundance in NAFLD (NASH+SS) was independent of BMI and IR. NAFLD patients had higher concentrations of fecal propionate and isobutyric acid and serum 2-hydroxybutyrate and L-lactic acid. These findings suggest a potential role for a specific IM community and functional profile in the pathogenesis of NAFLD.
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              Data analysis for 16S microbial profiling from different benchtop sequencing platforms.

              Progress in microbial ecology is confounded by problems when evaluating results from different sequencing methodologies. Contrary to existing expectations, here we demonstrate that the same biological conclusion is reached using different NGS technologies when stringent sequence quality filtering and accurate clustering algorithms are applied.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: ResourcesRole: Writing – review & editing
                Role: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 April 2019
                2019
                : 14
                : 4
                : e0214582
                Affiliations
                [1 ] Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
                [2 ] Laboratory of Basic Research and Advanced Investigations in Neurosciences (BRAIN), Hospital de Clínicas de Porto Alegre, PortoAlegre, Rio Grande do Sul, Brazil
                [3 ] Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
                [4 ] Postgraduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
                [5 ] Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States of America
                [6 ] Interdisciplinary Research Center on Biotechnology-CIP-Biotec, Universidade Federal do Pampa, São Gabriel, Rio Grande do Sul, Brazil
                "INSERM", FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-1450-8828
                Article
                PONE-D-18-24856
                10.1371/journal.pone.0214582
                6445422
                30939160
                9f8edf5d-36e9-47a1-a0db-87160beb0df2
                © 2019 Colonetti et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 August 2018
                : 17 March 2019
                Page count
                Figures: 4, Tables: 2, Pages: 17
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
                Award ID: EDITAL PRONEX FAPERGS/CNPq 12/2014, processo 16/2551-0000492-7
                Award Recipient :
                Funded by: Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE-HCPA)
                Award ID: 150218
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Award ID: Finance Code 001
                Award Recipient :
                The present study was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)- EDITAL PRONEX FAPERGS/CNPq 12/2014, processo 16/2551-0000492-7; Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE-HCPA)- n. 150218 and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Clinical Genetics
                Genetic Diseases
                Autosomal Recessive Diseases
                Glycogen Storage Diseases
                Medicine and Health Sciences
                Metabolic Disorders
                Inherited Metabolic Disorders
                Glycogen Storage Diseases
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbiome
                Biology and Life Sciences
                Genetics
                Genomics
                Microbial Genomics
                Microbiome
                Biology and Life Sciences
                Microbiology
                Microbial Genomics
                Microbiome
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Inflammatory Bowel Disease
                Biology and Life Sciences
                Nutrition
                Diet
                Medicine and Health Sciences
                Nutrition
                Diet
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Biology and Life Sciences
                Organisms
                Bacteria
                Gut Bacteria
                Ruminococcus
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Carbohydrates
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Carbohydrates
                Custom metadata
                Raw sequences were deposited in the Sequence Read Archive (SRA), accession SRP093885. Records are accessible at https://www.ncbi.nlm.nih.gov/sra/SRP093885. Run numbers SRR7464574 to SRR7464613.

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                Uncategorized

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