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      Perturbation of the Human Microbiome as a Contributor to Inflammatory Bowel Disease

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          Abstract

          The human microbiome consist of the composite genome of native flora that have evolved with humanity over millennia and which contains 150-fold more genes than the human genome. A “healthy” microbiome plays an important role in the maintenance of health and prevention of illness, inclusive of autoimmune disease such as inflammatory bowel disease (IBD). IBD is a prevalent spectrum of disorders, most notably defined by Crohn’s disease (CD) and ulcerative colitis (UC), which are associated with considerable suffering, morbidity, and cost. This review presents an outline of the loss of a normal microbiome as an etiology of immune dysregulation and IBD pathogenesis initiation. We, furthermore, summarize the knowledge on the role of a healthy microbiome in terms of its diversity and important functional elements and, lastly, conclude with some of the therapeutic interventions and modalities that are now being explored as potential applications of microbiome-host interactions.

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          Most cited references75

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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

          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.
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            Time series community genomics analysis reveals rapid shifts in bacterial species, strains, and phage during infant gut colonization

            The gastrointestinal microbiome undergoes shifts in species and strain abundances, yet dynamics involving closely related microorganisms remain largely unknown because most methods cannot resolve them. We developed new metagenomic methods and utilized them to track species and strain level variations in microbial communities in 11 fecal samples collected from a premature infant during the first month of life. Ninety six percent of the sequencing reads were assembled into scaffolds of >500 bp in length that could be assigned to organisms at the strain level. Six essentially complete (∼99%) and two near-complete genomes were assembled for bacteria that comprised as little as 1% of the community, as well as nine partial genomes of bacteria representing as little as 0.05%. In addition, three viral genomes were assembled and assigned to their hosts. The relative abundance of three Staphylococcus epidermidis strains, as well as three phages that infect them, changed dramatically over time. Genes possibly related to these shifts include those for resistance to antibiotics, heavy metals, and phage. At the species level, we observed the decline of an early-colonizing Propionibacterium acnes strain similar to SK137 and the proliferation of novel Propionibacterium and Peptoniphilus species late in colonization. The Propionibacterium species differed in their ability to metabolize carbon compounds such as inositol and sialic acid, indicating that shifts in species composition likely impact the metabolic potential of the community. These results highlight the benefit of reconstructing complete genomes from metagenomic data and demonstrate methods for achieving this goal.
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              Smoking and inflammatory bowel disease: a meta-analysis.

              To assess whether there is a true effect of smoking on the 2 most prevalent forms of inflammatory bowel disease (IBD): Crohn disease (CD) and ulcerative colitis (UC). For this meta-analysis, we searched multiple health care databases, including MEDLINE and EMBASE (January 1980 to January 2006), to examine the relationship between smoking and IBD. Keywords searched included smoking, Inflammatory bowel disease, Crohn's disease, and ulcerative colitis. Data were abstracted using predefined inclusion and exclusion criteria. An odds ratio (OR) was recalculated for each study using the random-effects model, and a combined OR was calculated. A total of 245 articles were obtained through an electronic search of health care databases. Thirteen studies examined the relationship between UC and smoking, whereas 9 examined the relationship between CD and smoking. We found evidence of an association between current smoking and CD (OR, 1.76; 95% confidence interval [CI], 1.40-2.22) and former smoking and UC (OR, 1.79; 95% CI, 1.37-2.34). Current smoking had a protective effect on the development of UC when compared with controls (OR, 0.58; 95% CI, 0.45-0.75). This is the first meta-analysis, to our knowledge, to evaluate the relationship between smoking and IBD using accepted quality standards for meta-analysis reporting. Our meta-analyses confirm that smoking is an important environmental factor in IBD with differing effects in UC and CD. By using predefined inclusion criteria and testing for homogeneity, the current analysis provides an estimate of the effect of smoking on both these forms of IBD.
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                Author and article information

                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                30 June 2014
                September 2014
                : 3
                : 3
                : 510-527
                Affiliations
                [1 ]Department of Medicine, University of Calgary, Infection Prevention & Control, Alberta Health Services, Office 3685, 3500–26th Avenue Northeast, Calgary AB T1Y 6J4, Canada
                [2 ]Department of Production of Animal Health, University of Calgary, HSC 2521, Health Sciences Centre, 2500 University Drive Northwest, Calgary AB T2N 1N4, Canada; E-Mail: barkema@ 123456ucalgary.ca
                [3 ]Department of Medicine, University of Alberta, 7-142K Katz Building, Edmonton AB T6G 2E1, Canada; E-Mail: karen.madsen@ 123456ualberta.ca
                [4 ]Department of Medicine, University of Calgary, Alberta Health Services, Room 930, North Tower, Foothills Medical Centre, 1403–29th St NW, Calgary T2N 4J8, Canada; E-Mail: subrata.ghosh@ 123456albertahealthservices.ca
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: bayan.missaghi@ 123456albertahealthservices.ca ; Tel.: +1-403-943-4024; Fax: +1-403-291-2571.
                Article
                pathogens-03-00510
                10.3390/pathogens3030510
                4243426
                25438009
                415d2624-c246-41e6-89e2-2459afa9d4c5
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 26 March 2014
                : 06 June 2014
                : 09 June 2014
                Categories
                Review

                microbiota,metagenome,microbiome,inflammatory bowel disease,ulcerative colitis,crohn’s disease

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