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Extensive Modulation of the Fecal Metagenome in Children With Crohn's Disease During Exclusive Enteral Nutrition.

Quince C, Ijaz UZ, Loman N, Eren AM, Saulnier D, Russell J, Haig SJ, Calus ST, Quick J, Barclay A, Bertz M, Blaut M, Hansen R, McGrogan P, Russell RK, Edwards CA, Gerasimidis K - Am. J. Gastroenterol. (2015)

Bottom Line: OTUs that correlated positively or negatively with calprotectin decreased during EEN.The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN.Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.

View Article: PubMed Central - PubMed

Affiliation: Warwick Medical School, University of Warwick, Warwick, UK.

ABSTRACT

Objectives: Exploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn's disease (CD).

Methods: Fecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics.

Results: Microbial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN.

Conclusions: Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.

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Related in: MedlinePlus

Genus Shannon diversity, in richness equivalents (a), and non-metric multidimensional scaling (NMDS) of operational taxonomic unit (OTU) community structures (b) for each EEN sample time for the Crohn's disease (CD) children and healthy controls. (a) Diversity, in species equivalents, decreased during exclusive enteral nutrition (EEN; P=0.037) and was higher in healthy children vs. CD children at time A (P=0.009). (b) NMDS plot using Bray–Curtis distances of the 3% OTU community structures.
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fig1: Genus Shannon diversity, in richness equivalents (a), and non-metric multidimensional scaling (NMDS) of operational taxonomic unit (OTU) community structures (b) for each EEN sample time for the Crohn's disease (CD) children and healthy controls. (a) Diversity, in species equivalents, decreased during exclusive enteral nutrition (EEN; P=0.037) and was higher in healthy children vs. CD children at time A (P=0.009). (b) NMDS plot using Bray–Curtis distances of the 3% OTU community structures.

Mentions: The mean Shannon diversity, a measure of gut microbiota richness and evenness, was higher in controls than CD children prior to EEN (Controls vs. CD: 10.23 vs. 8.00; P=0.006; Figure 1). A higher diversity was observed using OTU than genus analysis. However, the reduction in diversity associated with CD was similar with both approaches (P=4.2 × 10−5, Supplementary Figure S1). In contrast, beta diversity, the variability of the OTU community structure between samples, was higher for CD children than healthy controls. This was apparent from Figure 1 but also using the betadisper function of the R vegan package. The dissimilarity of microbial community structure, among groups, expressed with the average Bray–Curtis distance for samples, was significantly higher in CD children (CD vs. Controls: 0.4913 vs. 0.4089; P=0.048). This effect was more significant using OTU analysis (CD vs. Controls: 0.5848 vs. 0.4868; P<0.001).


Extensive Modulation of the Fecal Metagenome in Children With Crohn's Disease During Exclusive Enteral Nutrition.

Quince C, Ijaz UZ, Loman N, Eren AM, Saulnier D, Russell J, Haig SJ, Calus ST, Quick J, Barclay A, Bertz M, Blaut M, Hansen R, McGrogan P, Russell RK, Edwards CA, Gerasimidis K - Am. J. Gastroenterol. (2015)

Genus Shannon diversity, in richness equivalents (a), and non-metric multidimensional scaling (NMDS) of operational taxonomic unit (OTU) community structures (b) for each EEN sample time for the Crohn's disease (CD) children and healthy controls. (a) Diversity, in species equivalents, decreased during exclusive enteral nutrition (EEN; P=0.037) and was higher in healthy children vs. CD children at time A (P=0.009). (b) NMDS plot using Bray–Curtis distances of the 3% OTU community structures.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697132&req=5

fig1: Genus Shannon diversity, in richness equivalents (a), and non-metric multidimensional scaling (NMDS) of operational taxonomic unit (OTU) community structures (b) for each EEN sample time for the Crohn's disease (CD) children and healthy controls. (a) Diversity, in species equivalents, decreased during exclusive enteral nutrition (EEN; P=0.037) and was higher in healthy children vs. CD children at time A (P=0.009). (b) NMDS plot using Bray–Curtis distances of the 3% OTU community structures.
Mentions: The mean Shannon diversity, a measure of gut microbiota richness and evenness, was higher in controls than CD children prior to EEN (Controls vs. CD: 10.23 vs. 8.00; P=0.006; Figure 1). A higher diversity was observed using OTU than genus analysis. However, the reduction in diversity associated with CD was similar with both approaches (P=4.2 × 10−5, Supplementary Figure S1). In contrast, beta diversity, the variability of the OTU community structure between samples, was higher for CD children than healthy controls. This was apparent from Figure 1 but also using the betadisper function of the R vegan package. The dissimilarity of microbial community structure, among groups, expressed with the average Bray–Curtis distance for samples, was significantly higher in CD children (CD vs. Controls: 0.4913 vs. 0.4089; P=0.048). This effect was more significant using OTU analysis (CD vs. Controls: 0.5848 vs. 0.4868; P<0.001).

Bottom Line: OTUs that correlated positively or negatively with calprotectin decreased during EEN.The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN.Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.

View Article: PubMed Central - PubMed

Affiliation: Warwick Medical School, University of Warwick, Warwick, UK.

ABSTRACT

Objectives: Exploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn's disease (CD).

Methods: Fecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics.

Results: Microbial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN.

Conclusions: Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.

Show MeSH
Related in: MedlinePlus