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Siblings of patients with Crohn’s disease exhibit a biologically relevant dysbiosis in mucosal microbial metacommunities
  1. Charlotte Hedin1,2,
  2. Christopher J van der Gast3,
  3. Geraint B Rogers4,
  4. Leah Cuthbertson3,
  5. Sara McCartney5,
  6. Andrew J Stagg2,
  7. James O Lindsay6,7,
  8. Kevin Whelan1
  1. 1Faculty of Life Sciences & Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, UK
  2. 2Centre for Immunology and Infectious Disease, Blizard Institute, Queen Mary University of London, London, UK
  3. 3NERC Centre for Ecology & Hydrology, Wallingford, Oxfordshire, UK
  4. 4South Australian Health and Medical Research Institute, Infection and Immunity Theme, Flinders University, Adelaide, Australia
  5. 5Centre for Gastroenterology and Nutrition, University College London, London, UK
  6. 6Centre for Digestive Diseases, Blizard Institute, Queen Mary University of London, London, UK
  7. 7Department of Gastroenterology, Barts Health NHS Trust, London, UK
  1. Correspondence to Professor Kevin Whelan, Faculty of Life Sciences & Medicine, Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK; kevin.whelan{at}


Objective To determine the existence of mucosal dysbiosis in siblings of patients with Crohn's disease (CD) using 454 pyrosequencing and to comprehensively characterise and determine the influence of genotypical and phenotypical factors, on that dysbiosis. Siblings of patients with CD have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. Whether the mucosal microbiota is disrupted in these at-risk individuals is unknown.

Design Rectal biopsy DNA was extracted from 21 patients with quiescent CD, 17 of their healthy siblings and 19 unrelated healthy controls. Mucosal microbiota was analysed by 16S rRNA gene pyrosequencing and were classified into core and rare species. Genotypical risk was determined using Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype by flow cytometry.

Results Core microbiota of both patients with CD and healthy siblings was significantly less diverse than controls. Metacommunity profiling (Bray–Curtis (SBC) index) showed the sibling core microbial composition to be more similar to CD (SBC=0.70) than to healthy controls, whereas the sibling rare microbiota was more similar to healthy controls (SBC=0.42). Faecalibacterium prausnitzii contributed most to core metacommunity dissimilarity both between siblings and controls, and between patients and controls. Phenotype/genotype markers of CD risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect.

Conclusions Individuals with elevated CD-risk display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. prausnitzii. This dysbiosis in healthy people at risk of CD implicates microbiological processes in CD pathogenesis.


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