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      Altered intestinal microbiota composition, antibiotic therapy and intestinal inflammation in children and adolescents with cystic fibrosis

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          Abstract

          The aim of the present study was to evaluate the effect of cystic fibrosis and antibiotic therapy on intestinal microbiota composition and intestinal inflammation in children and adolescents. A cross-sectional controlled study was conducted with 36 children and adolescents: 19 in the cystic fibrosis group (CFG) and 17 in the control group (CG) matched for age and sex. The CFG was subdivided based on the use of antibiotic therapy (CFAB group) and non-use of antibiotic therapy (CFnAB group). The following data were evaluated: colonization, antibiotic therapy, mutation, breastfeeding, use of infant formula, type of delivery, introduction of solid foods, body mass index, fecal calprotectin and intestinal microbiota composition (fluorescence in situ hybridization). Intestinal inflammation evaluated by fecal calprotectin was significantly higher in the CFG (median: 40.80 µg/g, IQR: 19.80–87.10, p = 0.040) and CFAB group (median: 62.95 µg/g, IQR: 21.80–136.62, p = 0.045) compared to the CG (median: 20.15 µg/g, IQR: 16.20–31.00), and the Bacteroides, Firmicutes, Eubacterium rectale and Faecalibacterium prausnitzii were significantly decreased (p < 0.05) in the CFG compared to the CG, whereas the bacteria Clostridium difficile, Escherichia coli and Pseudomonas aeruginosa were significantly increased in the CFG (p < 0.05). The main differences were found between the CG and CFAB group for Eubacterium rectale (p = 0.006), Bifidobacterium (p = 0.017), Escherichia coli (p = 0.030), Firmicutes (p = 0.002), Pseudomonas aeruginosa (p < 0.001) and Clostridium difficile (p = 0.006). The results of this study confirm intestinal inflammation in patients with CF, which may be related to changes in the composition of the intestinal microbiota.

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          Most cited references23

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          Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study.

          Dysbiosis of the infant gut microbiota may have long-term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut microbiota, and to explore whether breastfeeding modifies these effects.
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            Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era.

            Studies of metagenomics and the human microbiome will tremendously expand our knowledge of the composition of microbial communities in the human body. As our understanding of microbial variation and corresponding genetic parameters is refined, this information can be applied to rational remodeling or "tailoring" of human-associated microbial communities and their associated functions. Physiologic features such as the development of innate and adaptive immunity, relative susceptibilities to infections, immune tolerance, bioavailability of nutrients, and intestinal barrier function may be modified by changing the composition and functions of the microbial communities. The specialty of gastroenterology will be affected profoundly by the ability to modify the gastrointestinal microbiota through the rational deployment of antibiotics, probiotics, and prebiotics. Antibiotics might be used to remove or suppress undesirable components of the human microbiome. Probiotics can introduce missing microbial components with known beneficial functions for the human host. Prebiotics can enhance the proliferation of beneficial microbes or probiotics, to maximize sustainable changes in the human microbiome. Combinations of these approaches might provide synergistic and effective therapies for specific disorders. The human microbiome could be manipulated by such "smart" strategies to prevent and treat acute gastroenteritis, antibiotic-associated diarrhea and colitis, inflammatory bowel disease, irritable bowel syndrome, necrotizing enterocolitis, and a variety of other disorders.
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              The causes of intestinal dysbiosis: a review.

              Alterations in the bowel flora and its activities are now believed to be contributing factors to many chronic and degenerative diseases. Irritable bowel syndrome, inflammatory bowel disease, rheumatoid arthritis, and ankylosing spondylitis have all been linked to alterations in the intestinal microflora. The intestinal dysbiosis hypothesis suggests a number of factors associated with modern Western living have a detrimental impact on the microflora of the gastrointestinal tract. Factors such as antibiotics, psychological and physical stress, and certain dietary components have been found to contribute to intestinal dysbiosis. If these causes can be eliminated or at least attenuated then treatments aimed at manipulating the microflora may be more successful
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Methodology
                Role: ConceptualizationRole: Data curationRole: Methodology
                Role: Methodology
                Role: Methodology
                Role: Methodology
                Role: Formal analysisRole: Methodology
                Role: Formal analysisRole: Methodology
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 June 2018
                2018
                : 13
                : 6
                : e0198457
                Affiliations
                [1 ] Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Brazil
                [2 ] Department of Nutrition, Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Brazil
                [3 ] Department of Pathology, Federal University of Santa Catarina, Florianópolis, Brazil
                [4 ] Joana de Gusmão Children´s Hospital, Santa Catarina, Florianópolis, Brazil
                [5 ] Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
                Hospital for Sick Children, CANADA
                Author notes

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

                Author information
                http://orcid.org/0000-0002-9060-2288
                Article
                PONE-D-17-39432
                10.1371/journal.pone.0198457
                6014676
                29933382
                7c6d7e0b-d36e-44ed-81be-44dd2fc0e841
                © 2018 de Freitas 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
                : 6 November 2017
                : 18 May 2018
                Page count
                Figures: 2, Tables: 4, Pages: 14
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
                Award ID: 471197/2013-0
                Award Recipient :
                We thank the National Council for Scientific and Technological Development (CNPq) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for their financial support (#471197/2013-0) and scholarships for EAMM (#304281/2012-3); Programa de Bolsas de Estudo da Educação Superior de Santa Catarina (UNIEDU) for scholarships to MBF.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Medicine and Health Sciences
                Clinical Genetics
                Genetic Diseases
                Autosomal Recessive Diseases
                Cystic Fibrosis
                Biology and Life Sciences
                Developmental Biology
                Fibrosis
                Cystic Fibrosis
                Medicine and Health Sciences
                Pulmonology
                Cystic Fibrosis
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbiome
                Biology and Life Sciences
                Genetics
                Genomics
                Microbial Genomics
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                Biology and Life Sciences
                Organisms
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                Organisms
                Bacteria
                Gut Bacteria
                Clostridium Difficile
                Biology and Life Sciences
                Organisms
                Bacteria
                Gut Bacteria
                Bifidobacterium
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                Biology and Life Sciences
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                Research and Analysis Methods
                Experimental Organism Systems
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