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Original article
Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers
  1. A Lavelle1,2,
  2. G Lennon1,2,
  3. O O'Sullivan3,
  4. N Docherty4,
  5. A Balfe1,
  6. A Maguire2,
  7. H E Mulcahy2,
  8. G Doherty2,
  9. D O'Donoghue2,
  10. J Hyland2,
  11. R P Ross3,5,
  12. J C Coffey6,
  13. K Sheahan2,
  14. P D Cotter3,5,
  15. F Shanahan5,
  16. D C Winter1,2,
  17. P R O'Connell1,2
  1. 1University College Dublin, School of Medicine and Medical Science, Dublin, Ireland
  2. 2Centre for Colorectal Disease, Saint Vincent's University Hospital, Dublin, Ireland
  3. 3Teagasc, Food Research Centre, Moorepark, Fermoy, County Cork, Ireland
  4. 4Department of Physiology, Trinity College Dublin, Dublin, Ireland
  5. 5Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
  6. 64i Centre for Interventions in Infection, Inflammation and Immunity, Graduate Entry Medical School, University of Limerick, Limerick, Ireland
  1. Correspondence to Professor P Ronan O'Connell, School of Medicine and Medical Science, University College Dublin, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; Ronan.OConnell{at}ucd.ie

Abstract

Objectives The relevance of spatial composition in the microbial changes associated with UC is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in controls and UC.

Design A total of 98 samples were sequenced to a mean depth of 31 642 reads from nine individuals, four control volunteers undergoing routine colonoscopy and five patients undergoing surgical colectomy for medically-refractory UC. Samples were retrieved at four colorectal locations, incorporating the luminal microbiota, mucus gel layer and whole mucosal biopsies.

Results Interpersonal variability accounted for approximately half of the total variance. Surprisingly, within individuals, asymmetric Eigenvector map analysis demonstrated differentiation between the luminal and mucus gel microbiota, in both controls and UC, with no differentiation between colorectal regions. At a taxonomic level, differentiation was evident between both cohorts, as well as between the luminal and mucosal compartments, with a small group of taxa uniquely discriminating the luminal and mucosal microbiota in colitis. There was no correlation between regional inflammation and a breakdown in this spatial differentiation or bacterial diversity.

Conclusions Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked interpersonal variability. While elements of this structure overlap between UC and control volunteers, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxa.

  • COLONIC BACTERIA
  • INFLAMMATORY BOWEL DISEASE
  • INTESTINAL MICROBIOLOGY
  • ULCERATIVE COLITIS

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