title: High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease.
abstract: BACKGROUND
  The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles.
  
  
  RESULTS
  Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut.
  
  
  CONCLUSIONS
  These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. aw6@sanger.ac.uk
authors.forename: Alan W
authors.initials: AW
authors.lastname: Walker
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Sanderson
authors.forename: Carol
authors.initials: C
authors.lastname: Churcher
authors.forename: Gareth C
authors.initials: GC
authors.lastname: Parkes
authors.forename: Barry N
authors.initials: BN
authors.lastname: Hudspith
authors.forename: Neil
authors.initials: N
authors.lastname: Rayment
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brostoff
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Liljana
authors.initials: L
authors.lastname: Petrovska
mesh_terms: D000328:Adult; D000368:Aged; D058491:Bacterial Load; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000382:microbiology*; D003106:Colon / Q000382:microbiology*; D003424:Crohn Disease / Q000382:microbiology*; D004755:Enterobacteriaceae / Q000145:classification / Q000235:genetics; D005260:Female; D015723:Gene Library; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D055815:Young Adult
chemical_list: D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S