Nell S, Suerbaum S, Josenhans C.. The impact of the microbiota on the pathogenesis of IBD: lessons from mouse infection models. Nat Rev Micro 8: 564-577

Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Nature Reviews Microbiology (Impact Factor: 23.57). 08/2010; 8(8):564-77. DOI: 10.1038/nrmicro2403
Source: PubMed


Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a major
human health problem. The bacteria that live in the gut play an important part in the
pathogenesis of IBD. However, owing to the complexity of the gut microbiota, our understanding
of the roles of commensal and pathogenic bacteria in establishing a healthy intestinal barrier
and in its disruption is evolving only slowly. In recent years, mouse models of intestinal
inflammatory disorders based on defined bacterial infections have been used intensively to
dissect the roles of individual bacterial species and specific bacterial components in the
pathogenesis of IBD. In this Review, we focus on the impact of pathogenic and commensal bacteria
on IBD-like pathogenesis in mouse infection models and summarize important recent

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Available from: Sandra Nell, Mar 06, 2014
    • "Again, mouse models of intestinal inflammation have significantly improved our understanding of potential functions of individual bacterial species. Infection of mice with enteric pathogens has been demonstrated to cause chronic intestinal inflammation (Nell et al. 2010). Persistent infection of mice with the human commensal Bacteroides fragilis causes chronic colitis (Rhee et al. 2009). "
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    ABSTRACT: The intestinal microbiota has important metabolic and host-protective functions. Conversely to these beneficial functions, the intestinal microbiota is thought to play a central role in the etiopathogenesis of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), a chronic inflammation of the gut mucosa. Genetic screens and studies in experimental mouse models have clearly demonstrated that IBD can develop due to excessive translocation of bacteria into the bowel wall or dysregulated handling of bacteria in genetically susceptible hosts. In healthy individuals, the microbiota is efficiently separated from the mucosal immune system of the gut by the gut barrier, a single layer of highly specialized epithelial cells, some of which are equipped with innate immune functions to prevent or control access of bacterial antigens to the mucosal immune cells. It is currently unclear whether the composition of the microbial flora or individual bacterial strains or pathogens induces or supports the pathogenesis of IBD. Further research will be necessary to carefully dissect the contribution of individual bacterial species to this disease and to ascertain whether specific modulation of the intestinal microbiome may represent a valuable further option for future therapeutic strategies.
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    • "While important data have been generated from studies using mono-associated mice, results should also be interpreted with caution because, like GF mice, physiologic and immunologic processes in these mice may be very different when compared with mice raised with a complex microbiota (Chung et al. 2012). Moreover, as has been shown in several models of inflammatory bowel disease (reviewed in Nell et al. 2010), the presence of agents in isolation may modulate disease phenotypes very differently than when present in the context of other microbiota. As an example, IL-10-deficient mice raised in a conventional setting develop mild large intestinal inflammation that does not develop when these mice are raised GF (Sellon et al. 1998). "
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    ABSTRACT: Eukaryotic organisms are colonized by rich and dynamic communities of microbes, both internally (e.g., in the gastrointestinal and respiratory tracts) and externally (e.g., on skin and external mucosal surfaces). The vast majority of bacterial microbes reside in the lower gastrointestinal (GI) tract, and it is estimated that the gut of a healthy human is home to some 100 trillion bacteria, roughly an order of magnitude greater than the number of host somatic cells. The development of culture-independent methods to characterize the gut microbiota (GM) has spurred a renewed interest in its role in host health and disease. Indeed, associations have been identified between various changes in the composition of the GM and an extensive list of diseases, both enteric and systemic. Animal models provide a means whereby causal relationships between characteristic differences in the GM and diseases or conditions can be formally tested using genetically identical animals in highly controlled environments. Clearly, the GM and its interactions with the host and myriad environmental factors are exceedingly complex, and it is rare that a single microbial taxon associates with, much less causes, a phenotype with perfect sensitivity and specificity. Moreover, while the exact numbers are the subject of debate, it is well recognized that only a minority of gut bacteria can be successfully cultured ex vivo. Thus, to perform studies investigating causal roles of the GM in animal model phenotypes, researchers need clever techniques to experimentally manipulate the GM of animals, and several ingenious methods of doing so have been developed, each providing its own type of information and with its own set of advantages and drawbacks. The current review will focus on the various means of experimentally manipulating the GM of research animals, drawing attention to the factors that would aid a researcher in selecting an experimental approach, and with an emphasis on mice and rats, the primary model species used to evaluate the contribution of the GM to a disease phenotype. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email:
    Full-text · Article · Aug 2015 · ILAR journal / National Research Council, Institute of Laboratory Animal Resources
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    • "Dysbiosis of the microbiota favors bacterial translocation, increased pathogen burden, and excessive inflammation . The latter is clearly involved in the pathogenesis of inflammatory bowel diseases (Nell et al., 2010; Manichanh et al., 2012; Bringiotti et al., 2014). The central role of the intestinal microbiome (Preidis and Versalovic, 2009; Hollister et al., 2014) and the corresponding intestinal metabolome (Ursell et al., 2014) is clearly dependent on diet (Albenberg and Wu, 2014; Leone et al., 2013). "
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    ABSTRACT: Do food ecosystems feed gut ecosystems? And if so… fuel the immune system? Recent developments in metagenomics have provided researchers tools to open the "black box" of microbiome science. These novel technologies have enabled the establishment of correlations between dysbiotic microbial communities and many diseases. The complex interaction of the commensal microbiota with the immune system is a topic of substantial interest due to its relevance to health. The human gastrointestinal tract is composed of an immense number of resident and transient microorganisms. Both may play a direct and vital role in the maintenance of human health and well-being. An understanding of the interactions and mechanisms through which commensal and food-derived microbes shape host immunity and metabolism may yield new insights into the pathogenesis of many immune-mediated diseases. Consequently, by manipulating the contribution of food microbiota to the functionality of the gut ecosystem, there is great hope for development of new prophylactic and therapeutic interventions. This paper presents some insights and comments on the possible impact of exogenous fermented food microbes on the gut homeostasis. We shed light on the similar features shared by both fermented food microbes and probiotics. In particular, the key role of microbial strains as part of food ecosystems for health and diseases is discussed through the prism of fermented dairy products and gut inflammation. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Mar 2015 · International journal of food microbiology
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