Dataset Information

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: 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.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.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.

SUBMITTER: Walker AW

PROVIDER: S-EPMC3032643 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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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 AW Sanderson Jeremy D JD Churcher Carol C Parkes Gareth C GC Hudspith Barry N BN Rayment Neil N Brostoff Jonathan J Parkhill Julian J Dougan Gordon G Petrovska Liljana L

BMC microbiology 20110110

<h4>Background</h4>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 ...[more]

PMID: 21219646

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Project description:Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory disorder which comprises two main conditions: Crohn's disease (CD) and ulcerative colitis (UC). Although the etiology of IBD has not been fully elucidated, the gut microbiota is hypothesized to play a vital role in its development. The aim of this cross-sectional study was to characterize the fecal microbiota in CD or UC patients in a state of remission to reveal potential factors sustaining residual levels of inflammation and triggering disease relapses. Ninety-eight IBD patients in a state of clinical remission (66 UC, 32 CD) and 97 controls were recruited, and stool samples, as well as detailed patient data, were collected. After DNA extraction, the variable regions V1 and V2 of the 16S rRNA gene were amplified and sequenced. Patients with IBD had a decrease in alpha diversity compared to that of healthy controls, and the beta diversity indices showed dissimilarity between the cohorts. Healthy controls were associated with the beneficial organisms unclassified Akkermansia species (Akkermansia uncl.), Oscillibacter uncl., and Coprococcus uncl., while flavonoid-degrading bacteria were associated with IBD. Network analysis identified highly central and influential disease markers and a strongly correlated network module of Enterobacteriaceae which was associated with IBD and could act as drivers for residual inflammatory processes sustaining and triggering IBD, even in a state of low disease activity. The microbiota in IBD patients is significantly different from that of healthy controls, even in a state of remission, which implicates the microbiota as an important driver of chronicity in IBD. IMPORTANCE Dysbiosis in inflammatory bowel disease (IBD) has been implicated as a causal or contributory factor to the pathogenesis of the disease. This study, done on patients in remission while accounting for various confounding factors, shows significant community differences and altered community dynamics, even after acute inflammation has subsided. A cluster of Enterobacteriaceae was linked with Crohn's disease, suggesting that this cluster, which contains members known to disrupt colonization resistance and form biofilms, persists during quiescence and can lead to chronic inflammation. Flavonoid-degrading bacteria were also associated with IBD, raising the possibility that modification of dietary flavonoids might induce and maintain remission in IBD.

Dataset Information

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.

Publications

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.

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