Characterization of Microbiota in Children with Chronic Functional Constipation

• Published in: PloS one Vol. 11; no. 10; p. e0164731
• Main Authors: de Meij, Tim G. J., de Groot, Evelien F. J., Eck, Anat, Budding, Andries E., Kneepkens, C. M. Frank, Benninga, Marc A., van Bodegraven, Adriaan A., Savelkoul, Paul H. M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.10.2016; Public Library of Science (PLoS)
• Subjects: Adolescent; Bacteroides fragilis; Bacteroides ovatus; Bifidobacterium longum; Biodiversity; Biology and Life Sciences; Case-Control Studies; Child; Child, Preschool; Children; Chronic Disease; Comparative analysis; Constipation; Constipation - microbiology; Constipation - physiopathology; Deoxyribonucleic acid; Disease control; Diversity indices; DNA; Etiology; Feces; Female; Gastroenterology; Gastrointestinal agents; Gastrointestinal Microbiome; Health aspects; Hepatology; Humans; Infections; Intestinal microflora; Intestine; Irritable bowel syndrome; Lactobacillus reuteri; Laxatives; Male; Mathematical analysis; Median (statistics); Medicine and Health Sciences; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Motility; Optimization; Pediatrics; People and Places; Probiotics; Regression analysis; Rodents; Species; Species diversity; Statistical analysis; Statistical methods; Subgroups; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164731

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. 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. 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). 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.