title: Characterization of Microbiota in Children with Chronic Functional Constipation.
abstract: OBJECTIVE
  Disruption of the intestinal microbiota is considered an etiological factor in pediatric functional constipation. Scientifically based selection of potential beneficial probiotic strains in functional constipation therapy is not feasible due to insufficient knowledge of microbiota composition in affected subjects. The aim of this study was to describe microbial composition and diversity in children with functional constipation, compared to healthy controls.
  
  
  METHODS
  Fecal samples from 76 children diagnosed with functional constipation according to the Rome III criteria (median age 8.0 years; range 4.2-17.8) were analyzed by IS-pro, a PCR-based microbiota profiling method. Outcome was compared with intestinal microbiota profiles of 61 healthy children (median 8.6 years; range 4.1-17.9). Microbiota dissimilarity was depicted by principal coordinate analysis (PCoA), diversity was calculated by Shannon diversity index. To determine the most discriminative species, cross validated logistic ridge regression was performed.
  
  
  RESULTS
  Applying total microbiota profiles (all phyla together) or per phylum analysis, no disease-specific separation was observed by PCoA and by calculation of diversity indices. By ridge regression, however, functional constipation and controls could be discriminated with 82% accuracy. Most discriminative species were Bacteroides fragilis, Bacteroides ovatus, Bifidobacterium longum, Parabacteroides species (increased in functional constipation) and Alistipes finegoldii (decreased in functional constipation).
  
  
  CONCLUSIONS
  None of the commonly used unsupervised statistical methods allowed for microbiota-based discrimination of children with functional constipation and controls. By ridge regression, however, both groups could be discriminated with 82% accuracy. Optimization of microbiota-based interventions in constipated children warrants further characterization of microbial signatures linked to clinical subgroups of functional constipation.
authors.affiliation: Department of Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Tim G J
authors.initials: TG
authors.lastname: de Meij
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Evelien F J
authors.initials: EF
authors.lastname: de Groot
authors.affiliation: Department of Medical Microbiology & Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Anat
authors.initials: A
authors.lastname: Eck
authors.affiliation: Department of Medical Microbiology & Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Andries E
authors.initials: AE
authors.lastname: Budding
authors.affiliation: Department of Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: C M Frank
authors.initials: CM
authors.lastname: Kneepkens
authors.affiliation: Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Benninga
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Center, Heerlen-Sittard-Geleen, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: van Bodegraven
authors.affiliation: Department of Medical Microbiology & Infection Control, VU University Medical Center, Amsterdam, The Netherlands.|Department of Medical Microbiology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Paul H M
authors.initials: PH
authors.lastname: Savelkoul
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003248:Constipation / Q000382:microbiology* / Q000503:physiopathology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008297:Male