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

Alan W Walker, Jeremy D Sanderson, Carol Churcher, Gareth C Parkes, Barry N Hudspith, Neil Rayment, Jonathan Brostoff, Julian Parkhill, Gordon Dougan, Liljana Petrovska

Research output: Contribution to journalArticle

344 Citations (Scopus)
4 Downloads (Pure)

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.
Original languageEnglish
Article number7
Number of pages12
JournalBioMed Central Microbiology
Volume11
DOIs
Publication statusPublished - 10 Jan 2011

Fingerprint

Dysbiosis
Microbiota
Inflammatory Bowel Diseases
Crohn Disease
Intestines
Mucous Membrane
Clone Cells
Ulcerative Colitis
Bacteroidetes
Biopsy
Enterobacteriaceae
rRNA Genes
Colon
Maintenance
Inflammation
Bacteria

Keywords

  • adult
  • aged
  • bacterial load
  • biopsy
  • case-control studies
  • colitis, ulcerative
  • colon
  • Crohn disease
  • enterobacteriaceae
  • female
  • gene library
  • humans
  • intestinal mucosa
  • male
  • metagenome
  • middle aged
  • RNA, bacterial
  • RNA, ribosomal, 16S
  • young adult

Cite this

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. / Walker, Alan W; Sanderson, Jeremy D; Churcher, Carol; Parkes, Gareth C; Hudspith, Barry N; Rayment, Neil; Brostoff, Jonathan; Parkhill, Julian; Dougan, Gordon; Petrovska, Liljana.

In: BioMed Central Microbiology, Vol. 11, 7, 10.01.2011.

Research output: Contribution to journalArticle

Walker, Alan W ; Sanderson, Jeremy D ; Churcher, Carol ; Parkes, Gareth C ; Hudspith, Barry N ; Rayment, Neil ; Brostoff, Jonathan ; Parkhill, Julian ; Dougan, Gordon ; Petrovska, Liljana. / 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. In: BioMed Central Microbiology. 2011 ; Vol. 11.
@article{23a170103bda46f8b868d83fbfee6874,
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 = "BackgroundThe 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.ResultsPaired 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.ConclusionsThese 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.",
keywords = "adult, aged, bacterial load, biopsy, case-control studies, colitis, ulcerative, colon, Crohn disease, enterobacteriaceae, female, gene library, humans, intestinal mucosa, male, metagenome, middle aged, RNA, bacterial, RNA, ribosomal, 16S, young adult",
author = "Walker, {Alan W} and Sanderson, {Jeremy D} and Carol Churcher and Parkes, {Gareth C} and Hudspith, {Barry N} and Neil Rayment and Jonathan Brostoff and Julian Parkhill and Gordon Dougan and Liljana Petrovska",
year = "2011",
month = "1",
day = "10",
doi = "10.1186/1471-2180-11-7",
language = "English",
volume = "11",
journal = "BioMed Central Microbiology",
issn = "1471-2180",
publisher = "BioMed Central",

}

TY - JOUR

T1 - 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

AU - Walker, Alan W

AU - Sanderson, Jeremy D

AU - Churcher, Carol

AU - Parkes, Gareth C

AU - Hudspith, Barry N

AU - Rayment, Neil

AU - Brostoff, Jonathan

AU - Parkhill, Julian

AU - Dougan, Gordon

AU - Petrovska, Liljana

PY - 2011/1/10

Y1 - 2011/1/10

N2 - BackgroundThe 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.ResultsPaired 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.ConclusionsThese 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.

AB - BackgroundThe 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.ResultsPaired 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.ConclusionsThese 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.

KW - adult

KW - aged

KW - bacterial load

KW - biopsy

KW - case-control studies

KW - colitis, ulcerative

KW - colon

KW - Crohn disease

KW - enterobacteriaceae

KW - female

KW - gene library

KW - humans

KW - intestinal mucosa

KW - male

KW - metagenome

KW - middle aged

KW - RNA, bacterial

KW - RNA, ribosomal, 16S

KW - young adult

U2 - 10.1186/1471-2180-11-7

DO - 10.1186/1471-2180-11-7

M3 - Article

C2 - 21219646

VL - 11

JO - BioMed Central Microbiology

JF - BioMed Central Microbiology

SN - 1471-2180

M1 - 7

ER -