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OC-011 Demographic, clinical and genetic factors associated with dysbiosis in patients with active Crohn's disease
  1. J L Benjamin1,
  2. A Koutsoumpas1,
  3. C R H Hedin1,
  4. S C Ng2,
  5. N J Prescott3,
  6. P Pessoa-Lopes3,
  7. C G Mathew3,
  8. M A Kamm2,
  9. A L Hart2,
  10. J D Sanderson1,
  11. S C Knight2,
  12. A Forbes4,
  13. A J Stagg5,
  14. J O Lindsay6,
  15. K Whelan1
  1. 1Nutritional Sciences Division, King's College London, London, UK
  2. 2Antigen Presenting Research Group, Imperial College, London, UK
  3. 3Department of Medical and Molecular Genetics, King's College London, London, UK
  4. 4Centre for Gastroenterology and Nutrition, University College, UK
  5. 5The Blizard Institute of Cell and Molecular Science, UK
  6. 6Digestive Disease Clinical Academic Unit, Barts and the London School of Medicine, London, UK

Abstract

Introduction Crohn's Disease (CD) is associated with an intestinal dysbiosis. The major bacterial group bacteroides may be associated with inflammation, while bifidobacteria and Faecalibacterium prausnitzii are immuno-regulatory. The NOD2 and autophagy genes, which code for bacterial recognition receptors, supports the role for the intestinal microbiota in CD. In addition, smoking results in more severe CD, while ileal involvement results in higher rates of surgical resection.

Methods The aim was to investigate the demographic, clinical and genetic factors associated with dysbiosis in CD. Patients (n=101) with active CD (CDAI≥220) were recruited. Demographic and clinical information was collected. Blood samples were taken for genotyping of NOD2, IRGM and ATG16L1 genes. Faecal samples were collected and analysed by fluorescent in situ hybridisation, using a DNA stain for total cells and fluorescently labelled probes targeting 16S rRNA of bifidobacteria, bacteroides, Lactobacillus, E coli and F prausnitzii.

Results Smokers (n=29) had significantly higher proportions of bacteroides (mean 38.8%, SD 13.7) compared with non-smokers (n=72) (28.33%, 12.6, p<0.001). The lower concentrations of F prausnitzii in smokers (mean 8.4, SD 0.9 log10 cells/g) compared with non-smokers (8.8, 1.0 log10 cells/g), approached significance (p=0.09). There were higher proportions of bacteroides in the 78 patients with ileal involvement (mean 32.7%, SD 14.2) compared with 23 patients without (26.6%, 10.8, p=0.058). Patients with ileal involvement also had lower proportions (mean 7.0%, SD 11.0 vs 18.1%, 20.0, p=0.001) and concentrations (mean 8.5, SD 1.0 vs 9.3, 0.7 log10 cells/g, p<0.001) of F prausnitzii compared to those without. Risk variants in NOD2 or ATG16L1 genes were not associated with differences in bacteria. Patients who had risk variants in the IRGM gene had lower proportions of bifidobacteria compared to those without (mean 14.8%, SD 8.2 vs 20.7%, 16.7, p=0.078), approaching significance.

Conclusion Smokers and patients with ileal involvement have luminal microbiota consisting of significantly higher bacteroides and lower immuno-regulatory F prausnitzii. This may indicate a potential mechanism through which the negative effects of smoking on Crohn's disease are mediated.

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