title: Long Term Development of Gut Microbiota Composition in Atopic Children: Impact of Probiotics.
abstract: BACKGROUND
  Imbalance of the human gut microbiota in early childhood is suggested as a risk factor for immune-mediated disorders such as allergies. With the objective to modulate the intestinal microbiota, probiotic supplementation during infancy has been used for prevention of allergic diseases in infants, with variable success. However, not much is known about the long-term consequences of neonatal use of probiotics on the microbiota composition. The aim of this study was to assess the composition and microbial diversity in stool samples of infants at high-risk for atopic disease, from birth onwards to six years of age, who were treated with probiotics or placebo during the first year of life.
  
  
  METHODS
  In a double-blind, randomized, placebo-controlled trial, a probiotic mixture consisting of B. bifidum W23, B. lactis W52 and Lc. Lactis W58 (Ecologic® Panda) was administered to pregnant women during the last 6 weeks of pregnancy and to their offspring during the first year of life. During follow-up, faecal samples were collected from 99 children over a 6-year period with the following time points: first week, second week, first month, three months, first year, eighteen months, two years and six years. Bacterial profiling was performed by IS-pro. Differences in bacterial abundance and diversity were assessed by conventional statistics.
  
  
  RESULTS
  The presence of the supplemented probiotic strains in faecal samples was confirmed, and the probiotic strains had a higher abundance and prevalence in the probiotic group during supplementation. Only minor and short term differences in composition of microbiota were found between the probiotic and placebo group and between children with or without atopy. The diversity of Bacteroidetes was significantly higher after two weeks in the placebo group, and at the age of two years atopic children had a significantly higher Proteobacteria diversity (p < 0.05). Gut microbiota development continued between two and six years, whereby microbiota composition at phylum level evolved more and more towards an adult-like configuration.
  
  
  CONCLUSIONS
  Perinatal supplementation with Ecologic® Panda, to children at high-risk for atopic disease, had minor effects on gut microbiota composition during the supplementation period. No long lasting differences were identified. Regardless of intervention or atopic disease status, children had a shared microbiota development over time determined by age that continued to develop between two and six years.
authors.affiliation: Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, the Netherlands; Department of Pediatrics, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: N B M M
authors.initials: NB
authors.lastname: Rutten
authors.affiliation: Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, the Netherlands.
authors.forename: D M W
authors.initials: DM
authors.lastname: Gorissen
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Eck
authors.affiliation: Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, the Netherlands.
authors.forename: L E M
authors.initials: LE
authors.lastname: Niers
authors.affiliation: Department of Pediatrics, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Vlieger
authors.affiliation: Winclove Probiotics BV, Amsterdam, the Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Besseling-van der Vaart
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: A E
authors.initials: AE
authors.lastname: Budding
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, the Netherlands; Department of Medical Microbiology, School of Nutrition & Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: P H M
authors.initials: PH
authors.lastname: Savelkoul
authors.affiliation: Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, the Netherlands.
authors.forename: C K
authors.initials: CK
authors.lastname: van der Ent
authors.affiliation: Department of Sciences, University College Roosevelt Academy, Middelburg and Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: G T
authors.initials: GT
authors.lastname: Rijkers
mesh_terms: D015373:Bacterial Typing Techniques; D001644:Bifidobacterium; D044822:Biodiversity; D002648:Child; D002675:Child, Preschool; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D007778:Lactobacillus; D008297:Male; D054892:Metagenome / Q000235:genetics*; D010919:Placebos / Q000627:therapeutic use; D011247:Pregnancy; D019936:Probiotics / Q000627:therapeutic use*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000235:genetics
chemical_list: D010919:Placebos; D012336:RNA, Ribosomal, 16S; D012338:RNA, Ribosomal, 23S