Characterization of Microbiota in Children with Chronic Functional Constipation

Tim G J de Meij, Evelien F J de Groot, Andries E Budding, C M Frank Kneepkens, Marc A Benninga, Adriaan A van Bodegraven, Paul H M Savelkoul, A Eck Hauer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVES: 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.

STUDY DESIGN: 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.

Original languageEnglish
Pages (from-to)e0164731
JournalPLoS ONE
Volume11
Issue number10
DOIs
Publication statusPublished - 2016

Cite this

de Meij, Tim G J ; de Groot, Evelien F J ; Budding, Andries E ; Kneepkens, C M Frank ; Benninga, Marc A ; van Bodegraven, Adriaan A ; Savelkoul, Paul H M ; Eck Hauer, A. / Characterization of Microbiota in Children with Chronic Functional Constipation. In: PLoS ONE. 2016 ; Vol. 11, No. 10. pp. e0164731.
@article{113d0dbc06d3490abe2f074b68ac2d5f,
title = "Characterization of Microbiota in Children with Chronic Functional Constipation",
abstract = "OBJECTIVES: 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.STUDY DESIGN: 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.",
author = "{de Meij}, {Tim G J} and {de Groot}, {Evelien F J} and Budding, {Andries E} and Kneepkens, {C M Frank} and Benninga, {Marc A} and {van Bodegraven}, {Adriaan A} and Savelkoul, {Paul H M} and {Eck Hauer}, A",
year = "2016",
doi = "10.1371/journal.pone.0164731",
language = "English",
volume = "11",
pages = "e0164731",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

Characterization of Microbiota in Children with Chronic Functional Constipation. / de Meij, Tim G J; de Groot, Evelien F J; Budding, Andries E; Kneepkens, C M Frank; Benninga, Marc A; van Bodegraven, Adriaan A; Savelkoul, Paul H M; Eck Hauer, A.

In: PLoS ONE, Vol. 11, No. 10, 2016, p. e0164731.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Characterization of Microbiota in Children with Chronic Functional Constipation

AU - de Meij, Tim G J

AU - de Groot, Evelien F J

AU - Budding, Andries E

AU - Kneepkens, C M Frank

AU - Benninga, Marc A

AU - van Bodegraven, Adriaan A

AU - Savelkoul, Paul H M

AU - Eck Hauer, A

PY - 2016

Y1 - 2016

N2 - OBJECTIVES: 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.STUDY DESIGN: 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.

AB - OBJECTIVES: 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.STUDY DESIGN: 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.

U2 - 10.1371/journal.pone.0164731

DO - 10.1371/journal.pone.0164731

M3 - Article

VL - 11

SP - e0164731

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 10

ER -