For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
57
views
65
references
 Top references
cited by
112
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      0
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      A Multihit Model: Colitis Lessons from the Interleukin-10–deficient Mouse

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Article first published online 3 July 2015

          Abstract:

          Complex mechanisms are pulling the strings to initiate the development of inflammatory bowel disease. Current evidence indicates that an interaction of genetic susceptibilities (polymorphisms), environmental factors, and the host microbiota leads to a dysregulation of the mucosal immune system. In the past decades, the interleukin-10–deficient mouse has served as an excellent model to mirror the multifactorial nature of this disease. Here, we want to review in detail the interplay of the genetic factors, immune aspects, and especially summarize and discuss the role of the microbiota contributing to colitis development in the interleukin-10–deficient mouse model of inflammatory bowel disease as a multihit model.

          Related collections

          Most cited references65

          • Record: found
          • Abstract: found
          • Article: not found

          A microbial symbiosis factor prevents intestinal inflammatory disease.

          Sarkis Mazmanian, June Round, Dennis Kasper (2008)
          Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.
          Article 0 comments Cited 785 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The microbiome in inflammatory bowel disease: current status and the future ahead.

            Aleksandar D. Kostic, Ramnik Xavier, Dirk Gevers (2014)
            Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system. Enhanced technologies can increase our understanding of the interactions between the host and its resident microbiota and their respective roles in IBD from both a large-scale pathway view and at the metabolic level. We review important microbiome studies of patients with IBD and describe what we have learned about the mechanisms of intestinal microbiota dysfunction. We describe the recent progress in microbiome research from exploratory 16S-based studies, reporting associations of specific organisms with a disease, to more recent studies that have taken a more nuanced view, addressing the function of the microbiota by metagenomic and metabolomic methods. Finally, we propose study designs and methodologies for future investigations of the microbiome in patients with inflammatory gut and autoimmune diseases in general. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
            Article 0 comments Cited 689 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              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 Sanderson, Carol Churcher … (2011)
              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.
              Article 0 comments Cited 278 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Inflamm Bowel Dis
                Journal ID (iso-abbrev): Inflamm. Bowel Dis
                Journal ID (publisher-id): ibd
                Title: Inflammatory Bowel Diseases
                Publisher: Lippincott Williams & Wilkins
                ISSN (Print): 1078-0998
                ISSN (Electronic): 1536-4844
                Publication date (Electronic): 03 July 2015
                Publication date (Print): August 2015
                Volume: 21
                Issue: 8
                Pages: 1967-1975
                Affiliations
                Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
                Author notes
                Reprints: André Bleich, PhD, Institute for Laboratory Animal Science, Hannover Medical School, Carl-Neuberg-Street 1, 30625 Hannover, Germany (e-mail: bleich.andre@ 123456mh-hannover.de ).
                Article
                Publisher ID: IBD-15-0183 Accession ID: 00029
                DOI: 10.1097/MIB.0000000000000468
                PMC ID: 4511684
                PubMed ID: 26164667
                SO-VID: ea760267-34ea-43d9-a88a-051605664a88
                Copyright © Copyright © 2015 Crohn's & Colitis Foundation of America, Inc.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

                History
                Date received : 11 March 2015
                Date accepted : 3 April 2015
                Categories
                Subject: Basic Science Review Articles
                Custom metadata
                OPEN-ACCESS TRUE

                ScienceOpen disciplines: Gastroenterology & Hepatology
                Keywords: colitis,disease susceptibility,ibd,interleukin-10-deficient mouse,microbiota,microflora
                Data availability:
                ScienceOpen disciplines: Gastroenterology & Hepatology
                Keywords: colitis, disease susceptibility, ibd, interleukin-10-deficient mouse, microbiota, microflora

                Comments

                Comment on this article