title: Siblings of patients with Crohn's disease exhibit a biologically relevant dysbiosis in mucosal microbial metacommunities.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Faculty of Life Sciences & Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, UK Centre for Immunology and Infectious Disease, Blizard Institute, Queen Mary University of London, London, UK.
authors: Charlotte
authors: C
authors: Hedin
authors: NERC Centre for Ecology & Hydrology, Wallingford, Oxfordshire, UK.
authors: Christopher J
authors: CJ
authors: van der Gast
authors: South Australian Health and Medical Research Institute, Infection and Immunity Theme, Flinders University, Adelaide, Australia.
authors: Geraint B
authors: GB
authors: Rogers
authors: NERC Centre for Ecology & Hydrology, Wallingford, Oxfordshire, UK.
authors: Leah
authors: L
authors: Cuthbertson
authors: Centre for Gastroenterology and Nutrition, University College London, London, UK.
authors: Sara
authors: S
authors: McCartney
authors: Centre for Immunology and Infectious Disease, Blizard Institute, Queen Mary University of London, London, UK.
authors: Andrew J
authors: AJ
authors: Stagg
authors: Centre for Digestive Diseases, Blizard Institute, Queen Mary University of London, London, UK Department of Gastroenterology, Barts Health NHS Trust, London, UK.
authors: James O
authors: JO
authors: Lindsay
authors: Faculty of Life Sciences & Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, UK.
authors: Kevin
authors: K
authors: Whelan
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics / Q000382:microbiology* / Q000473:pathology*; D064806:Dysbiosis / Q000382:microbiology*; D000070037:Faecalibacterium prausnitzii / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D005260:Female; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D007422:Intestines / Q000382:microbiology; D008297:Male; D064307:Microbiota; D010641:Phenotype; D035781:Siblings
keywords: BACTERIAL PATHOGENESIS; CROHN'S DISEASE; GENOTYPE; INFLAMMATORY BOWEL DISEASE