A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis.

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Abstract

Bacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's disease (CD), in which dysbiosis has been better characterised, in ulcerative colitis (UC), only small cohorts have been studied and showed conflicting data. Therefore, we evaluated in a large cohort if the microbial signature described in CD is also present in UC, and if we could characterise predominant dysbiosis in UC. To assess the functional impact of dysbiosis, we quantified the bacterial metabolites.

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Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.

H Sokol, B Pigneur, L. Watterlot … (2008)

A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-kappaB activity, F. prausnitzii had no effect on IL-1beta-induced NF-kappaB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-gamma production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-kappaB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.

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Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Luke Jostins, Stephan Ripke, Rinse Weersma … (2013)

Crohn’s disease (CD) and ulcerative colitis (UC), the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry with rising prevalence in other populations 1 . Genome-wide association studies (GWAS) and subsequent meta-analyses of CD and UC 2,3 as separate phenotypes implicated previously unsuspected mechanisms, such as autophagy 4 , in pathogenesis and showed that some IBD loci are shared with other inflammatory diseases 5 . Here we expand knowledge of relevant pathways by undertaking a meta-analysis of CD and UC genome-wide association scans, with validation of significant findings in more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional and balancing selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe striking overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

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Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases.

D Frank, A. St. Amand, R Feldman … (2007)

The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.

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Author and article information

Journal

Journal ID (iso-abbrev): Gut

Title: Gut

Publisher: BMJ

ISSN (Electronic): 1468-3288

ISSN (Print): 0017-5749

Publication date (Electronic): Aug 2014

Volume: 63

Issue: 8

Affiliations

[1 ] Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.

[2 ] Department of Structural Biology, VIB-Vrije Universiteit Brussel, Brussels, Belgium Department of Applied Biological Sciences (DBIT), Vrije Universiteit Brussel, Brussels, Belgium.

[3 ] Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.

[4 ] Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

[5 ] Department of Clinical Microbiology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.

Article

Publisher Item ID: gutjnl-2013-304833

DOI: 10.1136/gutjnl-2013-304833

PubMed ID: 24021287

SO-VID: 4fd66367-0c0b-4892-8ace-abf36ddecac6

History

Keywords: ULCERATIVE COLITIS,INTESTINAL BACTERIA

Data availability:

Keywords: ULCERATIVE COLITIS, INTESTINAL BACTERIA

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A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis.

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Most cited references 50

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases.

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