Metagenomic Approaches for Defining the Pathogenesis of Inflammatory Bowel Diseases

Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108, USA.
Cell host & microbe (Impact Factor: 12.33). 07/2008; 3(6):417-27. DOI: 10.1016/j.chom.2008.05.001
Source: PubMed


The human gastrointestinal tract is home to immense and complex populations of microorganisms. Using recent technical innovations, the diversity present in this human body habitat is now being analyzed in detail. This review focuses on the microbial ecology of the gut in inflammatory bowel diseases and on how recent studies provide an impetus for using carefully designed, comparative metagenomic approaches to delve into the structure and activities of the gut microbial community and its interrelationship with the immune system.

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Available from: Daniel A Peterson, Apr 01, 2014
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    • "Altered diversity and abundance of the so-called 'normal flora' during disease development and progression were unknown before the introduction of metagenomic sequencing, since most of these organisms are non-culturable. 16S rRNA sequencing has indicated a decrease in Bacteroides and Firmicutes numbers in the colon and an increase in Enterobacteriaceae, such as adherent-invasive E. coli and other Proteobacteria in Crohn's disease [60]. In contrast, obesity is associated with fermenting bacterial species, such as Bacteroides and Firmicutes, which can harvest energy from complex polysaccharides [54]. "
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    ABSTRACT: Gut microbiota of higher vertebrates is host-specific. The number and diversity of the organisms residing within the gut ecosystem are defined by physiological and environmental factors, such as host genotype, habitat, and diet. Recently, culture-independent sequencing techniques have added a new dimension to the study of gut microbiota and the challenge to analyze the large volume of sequencing data is increasingly addressed by the development of novel computational tools and methods. Interestingly, gut microbiota maintains a constant relative abundance at operational taxonomic unit (OTU) levels and altered bacterial abundance has been associated with complex diseases such as symptomatic atherosclerosis, type 2 diabetes, obesity, and colorectal cancer. Therefore, the study of gut microbial population has emerged as an important field of research in order to ultimately achieve better health. In addition, there is a spontaneous, non-linear, and dynamic interaction among different bacterial species residing in the gut. Thus, predicting the influence of perturbed microbe-microbe interaction network on health can aid in developing novel therapeutics. Here, we summarize the population abundance of gut microbiota and its variation in different clinical states, computational tools available to analyze the pyrosequencing data, and gut microbe-microbe interaction networks. Copyright © 2015. Production and hosting by Elsevier Ltd.
    07/2015; 13(3). DOI:10.1016/j.gpb.2015.02.005
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    • "Stool is regularly characterized by an expansion of Firmicutes relative to Proteobacteria and Bacteroidetes at the mucosal surface, and the heterogeneity of the microbiome within individual stool samples is not yet well understood. Additionally, the biogeography of the intestinal tract itself influences microbial community structure and function, with dramatic differences in pH, microbial density , and composition between the small and large intestine and in a more gradual continuum across the colon (Eckburg et al., 2005; Morgan et al., 2012; Peterson et al., 2008; Stearns et al., 2011). Diffusion rates of microbes, microbial metabolites, and host biomolecules through the mucosa and lumen are generally not well characterized, making their biogeographical sources and sinks somewhat unclear. "
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    ABSTRACT: The inflammatory bowel diseases (IBDs) are among the most closely studied chronic inflammatory disorders that involve environmental, host genetic, and commensal microbial factors. This combination of features has made IBD both an appropriate and a high-priority platform for translatable research in host-microbiome interactions. Decades of epidemiology have identified environmental risk factors, although most mechanisms of action remain unexplained. The genetic architecture of IBD has been carefully dissected in multiple large populations, identifying several responsible host epithelial and immune pathways but without yet a complete systems-level explanation. Most recently, the commensal gut microbiota have been found to be both ecologically and functionally perturbed during the disease, but with as-yet-unexplained heterogeneity among IBD subtypes and individual patients. IBD thus represents perhaps the most comprehensive current model for understanding the human microbiome's role in complex inflammatory disease. Here, we review the influences of the microbiota on IBD and its potential for translational medicine.
    Immunity 06/2014; 40(6):843-854. DOI:10.1016/j.immuni.2014.05.013 · 21.56 Impact Factor
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    • "Fig. 4. Distribution of predominant bacterial phylotypes in the human intestinal tract. Relative abundance is illustrated as a function of location along the healthy and inflamed small bowel (ileum) and colon (reproduced from Ref. [92], with permission). Table 1 Changes in lifestyle may alter the intestinal microbiota. "
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    ABSTRACT: The mammalian intestine encounters many more microorganisms than any other tissue in the body thus making it the largest and most complex component of the immune system. Indeed, there are greater than 100 trillion (10(14)) microbes within the healthy human intestine where the total number of genes derived from this diverse microbiome exceeds that of the entire human genome by at least 100-fold. Our coexistence with the gut microbiota represents a dynamic and mutually beneficial relationship that is thought to be a major determinant of health and disease. Because of the potential for intestinal microorganisms to induce local and/or systemic inflammation, the intestinal immune system has developed a number of immune mechanisms to protect the host from pathogenic infections while limiting the inflammatory tissue injury that accompanies these immune responses. Failure to properly regulate intestinal mucosal immunity is thought to be responsible for the inflammatory tissue injury observed in the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis). An accumulating body of experimental and clinical evidence strongly suggest that IBD results from a dysregulated immune response to components of the normal gut flora in genetically-susceptible individuals. The objective of this review is to present our current understanding of the role that enteric microbiota play in intestinal homeostasis and pathogenesis of chronic intestinal inflammation.
    Free Radical Biology and Medicine 11/2013; 68. DOI:10.1016/j.freeradbiomed.2013.11.008 · 5.74 Impact Factor
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