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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

Log abundance of OTU3 (Bifidobacterium spp.) (a), OTU122 (Atopobium spp.) (b), and OTU4 (Ruminoccocus gnavus) (c) as a function of days on EEN discriminated by subject. Adjusted P-values: OTU122=0.0338; OTU3=0.00573; OTU4=0.0897. A full color version of this figure is available at the American Journal of Gastroenterology journal online. EEN, exclusive enteral nutrition; OTU, operational taxonomic unit.
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fig3: Log abundance of OTU3 (Bifidobacterium spp.) (a), OTU122 (Atopobium spp.) (b), and OTU4 (Ruminoccocus gnavus) (c) as a function of days on EEN discriminated by subject. Adjusted P-values: OTU122=0.0338; OTU3=0.00573; OTU4=0.0897. A full color version of this figure is available at the American Journal of Gastroenterology journal online. EEN, exclusive enteral nutrition; OTU, operational taxonomic unit.

Mentions: When relative abundance of each bacterial taxon, based on OTU and genus assignments, was regressed against days on EEN, allowing for a subject-dependent intercept, representing different starting abundances in different children, the vast majority of significant changes represented a reduction in relative abundance. Indeed, of 34 genera that significantly changed, only one, Lactococcus, increased with EEN (Table 2). Interestingly, some of the most negatively impacted genera were those whose abundance was already lower in CD children, before EEN initiation, than controls (e.g., Bifidobacterium, Ruminococcus, and Faecalibacterium). A similar impact was observed in OTU analysis (Supplementary Table S5), with a large number of OTUs decreasing during EEN. For example, OTU3, assigned to Bifidobacterium, decreased in some children by two logs of relative abundance (Figure 3), whereas OTU4, assigned to R. gnavus, increased in most subjects during EEN (Figure 3). Oligotyping of Lachnospiraceae confirmed these patterns, with all oligotypes significantly decreasing in abundance during EEN including oligotypes that were significantly higher or lower in CD (Supplementary Table S6).


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)

Log abundance of OTU3 (Bifidobacterium spp.) (a), OTU122 (Atopobium spp.) (b), and OTU4 (Ruminoccocus gnavus) (c) as a function of days on EEN discriminated by subject. Adjusted P-values: OTU122=0.0338; OTU3=0.00573; OTU4=0.0897. A full color version of this figure is available at the American Journal of Gastroenterology journal online. EEN, exclusive enteral nutrition; OTU, operational taxonomic unit.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Log abundance of OTU3 (Bifidobacterium spp.) (a), OTU122 (Atopobium spp.) (b), and OTU4 (Ruminoccocus gnavus) (c) as a function of days on EEN discriminated by subject. Adjusted P-values: OTU122=0.0338; OTU3=0.00573; OTU4=0.0897. A full color version of this figure is available at the American Journal of Gastroenterology journal online. EEN, exclusive enteral nutrition; OTU, operational taxonomic unit.
Mentions: When relative abundance of each bacterial taxon, based on OTU and genus assignments, was regressed against days on EEN, allowing for a subject-dependent intercept, representing different starting abundances in different children, the vast majority of significant changes represented a reduction in relative abundance. Indeed, of 34 genera that significantly changed, only one, Lactococcus, increased with EEN (Table 2). Interestingly, some of the most negatively impacted genera were those whose abundance was already lower in CD children, before EEN initiation, than controls (e.g., Bifidobacterium, Ruminococcus, and Faecalibacterium). A similar impact was observed in OTU analysis (Supplementary Table S5), with a large number of OTUs decreasing during EEN. For example, OTU3, assigned to Bifidobacterium, decreased in some children by two logs of relative abundance (Figure 3), whereas OTU4, assigned to R. gnavus, increased in most subjects during EEN (Figure 3). Oligotyping of Lachnospiraceae confirmed these patterns, with all oligotypes significantly decreasing in abundance during EEN including oligotypes that were significantly higher or lower in CD (Supplementary Table S6).

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