Microbiota of De-Novo Pediatric IBD: Increased Faecalibacterium Prausnitzii and Reduced Bacterial Diversity in Crohn's But Not in Ulcerative Colitis

Richard Hansen, Richard K Russell, Caroline Reiff, Petra Louis, Freda McIntosh, Susan H Berry, Indrani Mukhopadhya, W Michael Bisset, Andy R Barclay, Jon Bishop, Diana M Flynn, Paraic McGrogan, Sabarinathan Loganathan, Gamal Mahdi, Harry J Flint, Emad M El-Omar, Georgina L Hold

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Abstract

OBJECTIVES: The gastrointestinal microbiota is considered important in inflammatory bowel disease (IBD) pathogenesis. Discoveries from established disease cohorts report reduced bacterial diversity, changes in bacterial composition, and a protective role for Faecalibacterium prausnitzii in Crohn's disease (CD). The majority of studies to date are however potentially confounded by the effect of treatment and a reliance on established rather than de-novo disease.

METHODS: Microbial changes at diagnosis were examined by biopsying the colonic mucosa of 37 children: 25 with newly presenting, untreated IBD with active colitis (13 CD and 12 ulcerative colitis (UC)), and 12 pediatric controls with a macroscopically and microscopically normal colon. We utilized a dual-methodology approach with pyrosequencing (threshold >10,000 reads) and confirmatory real-time PCR (RT-PCR).

RESULTS: Threshold pyrosequencing output was obtained on 34 subjects (11 CD, 11 UC, 12 controls). No significant changes were noted at phylum level among the Bacteroidetes, Firmicutes, or Proteobacteria. A significant reduction in bacterial a-diversity was noted in CD vs. controls by three methods (Shannon, Simpson, and phylogenetic diversity) but not in UC vs. controls. An increase in Faecalibacterium was observed in CD compared with controls by pyrosequencing (mean 16.7% vs. 9.1% of reads, P=0.02) and replicated by specific F. prausnitzii RT-PCR (36.0% vs. 19.0% of total bacteria, P=0.02). No disease-specific clustering was evident on principal components analysis.

CONCLUSIONS: Our results offer a comprehensive examination of the IBD mucosal microbiota at diagnosis, unaffected by therapeutic confounders or changes over time. Our results challenge the current model of a protective role for F. prausnitzii in CD, suggesting a more dynamic role for this organism than previously described.

Original languageEnglish
Pages (from-to)1913-1922
Number of pages10
JournalAmerican journal of gastroenterology
Volume107
Issue number12
Early online date9 Oct 2012
DOIs
Publication statusPublished - 5 Dec 2012

Keywords

  • induction
  • inflammatory-bowel-disease
  • health
  • flora
  • human gut microbiota
  • remission
  • communities
  • nflammatory bowel disease, Crohn's Disease, ulcerative colitis
  • (Adolescent, Child, Clostridium, Colitis, Ulcerative, Colony Count, Microbial, Crohn Disease, Female, Humans, Inflammatory Bowel Diseases, Male, Real-Time Polymerase Chain Reaction, Journal Article, Research Support, Non-U.S. Gov't

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    Hansen, R., Russell, R. K., Reiff, C., Louis, P., McIntosh, F., Berry, S. H., Mukhopadhya, I., Bisset, W. M., Barclay, A. R., Bishop, J., Flynn, D. M., McGrogan, P., Loganathan, S., Mahdi, G., Flint, H. J., El-Omar, E. M., & Hold, G. L. (2012). Microbiota of De-Novo Pediatric IBD: Increased Faecalibacterium Prausnitzii and Reduced Bacterial Diversity in Crohn's But Not in Ulcerative Colitis. American journal of gastroenterology, 107(12), 1913-1922. https://doi.org/10.1038/ajg.2012.335