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. 2015 Jan 15;6(1):e71.
doi: 10.1038/ctg.2014.21.

Effect of exclusive enteral nutrition on the microbiota of children with newly diagnosed Crohn's disease

Nadeem O Kaakoush  1 , Andrew S Day  2 , Steven T Leach  3 , Daniel A Lemberg  4 , Shaun Nielsen  1 , Hazel M Mitchell  1
Affiliations

Effect of exclusive enteral nutrition on the microbiota of children with newly diagnosed Crohn's disease

Nadeem O Kaakoush et al. Clin Transl Gastroenterol. .

Abstract

Objectives: Exclusive enteral nutrition (EEN) is commonly used to treat pediatric Crohn's disease (CD). Meta-analysis of pediatric studies that have compared the effect of EEN with other treatments have shown that EEN induces remission in up to 80-85% of patients. We aimed to gain a comprehensive understanding of the effect of EEN on the microbiota of CD patients.

Methods: We used 16S rRNA gene and whole-genome high throughout sequencing to determine changes in the fecal microbiota of five CD children, before, during, and after EEN therapy and compared this with five healthy controls.

Results: The microbial diversity observed in CD patients tended to be lower than that in controls (CD: 2.25±0.24, controls: 2.75±0.14, P=0.11). In all CD patients, dysbiosis was observed prior to therapy. EEN therapy had a positive effect in all patients, with 80% going into remission. In some patients, the positive effect diminished following the conclusion of EEN therapy. Significantly, the number of operational taxonomic units (OTU) decreased dramatically upon starting EEN and this corresponded with CD remission. Recurrence of CD corresponded with an increase in OTUs. Six families within the Firmicutes were found to correlate with disease activity during and following EEN therapy, a finding that was confirmed by whole-genome high throughput sequencing.

Conclusions: Our results demonstrate that EEN leads to common and patient-specific alterations in the microbiota of CD patients, a number of which correlate with disease activity.

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Figures

Figure 1
Figure 1
Treatment and disease activity profiles of five children with Crohn's disease over 26 weeks. *Patient was classified as in remission, however, PCDAI was calculated to be 10. 5-ASA, 5-aminosalicyclic acid; AZA, azathioprine; EEN, exclusive enteral nutrition; MTZ, metronidazole; PCDAI, Pediatric Crohn's Disease Activity Index; SEN, supplementary enteral nutrition; SSZ, sulfasalazine.
Figure 2
Figure 2
Microbial profile of the healthy controls at the phylum level. (a) Average relative abundance (%) of bacterial taxa. (b) Standardized relative abundance levels (square root) of bacterial taxa. Abundance levels determined from method 2 were used.
Figure 3
Figure 3
Changes in the relative abundance of phyla in CD patients undergoing EEN therapy. (a) CD1, (b) CD2, (c) CD3, (d) CD4, and (e) CD5. Standardized relative abundance levels (square root) of bacterial taxa were plotted. Abundance levels determined from method 2 were used. Firmicutes (dark blue), Bacteroidetes (green), Proteobacteria (red), Actinobacteria (orange), Fusobacteria (light blue), and TM7 (yellow). CD, Crohn's disease; EEN, exclusive enteral nutrition.
Figure 4
Figure 4
Changes in the number of OTUs in the fecal microbiota of CD patients undergoing EEN therapy. (a) CD1, (b) CD2, (c) CD3, (d) CD4, and (e) CD5. Solid and dotted lines correspond to the number of OTUs from method 1 and method 2, respectively. CD, Crohn's disease; EEN, exclusive enteral nutrition; OTU, operational taxonomic unit.
Figure 5
Figure 5
Changes in the relative abundance of Firmicutes taxa in CD patients undergoing EEN therapy. (a) CD1, (b) CD2, (c) CD3, (d) CD4, and (e) CD5. Standardized relative abundance levels (square root) of bacterial taxa were plotted. Abundance levels determined from method 2 were used. Erysipelotrichaceae (dark blue), Ruminococcaceae (green), Lachnospiraceae (red), Streptococcaceae (orange), Veillonellaceae (light blue), and Peptostreptococcaceae (yellow). CD, Crohn's disease; EEN, exclusive enteral nutrition.
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