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      Enteric Virome and Bacterial Microbiota in Children With Ulcerative Colitis and Crohn Disease :

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          Abstract

          We examined the fecal enteric virome and bacterial community composition of children with Crohn’s disease (CD), ulcerative colitis (UC), and healthy controls to test the hypothesis that unique patterns of viral organisms and/or presence of bacterial pathogens may be identified that could contribute to the pathogenesis of pediatric inflammatory bowel disease (IBD). Fecal samples from 24 children (mean 12.2 years) with CD (n=7) or UC (n=5) and similar aged controls (n=12) were processed to determine individual viromes. Viral sequences were identified through translated protein sequence similarity search. Bacterial microbiota were determined by sequencing of the V4 region of the 16S rRNA gene. Only a few human viruses were detected, so virome analyses focused on bacterial viruses. The relative abundance of Caudovirales was greater than that of Microviridae phages in both IBD and healthy controls. Caudovirales phages were more abundant in CD (mean 80.8%) than UC (48.8%) (p=0.05) but not controls. The richness of viral strains in Microviridae but not Caudovirales was higher in controls than CD (p=0.05) but not UC cases. No other measure of phage abundance, richness, or Shannon diversity showed significant difference between the two IBD and control groups. Bacterial microbiota analysis revealed that IBD diagnosis, albumin, hemoglobin, erythrocyte sedimentation rate, and probiotic supplementation correlated to the composition of gut bacterial microbiota. Minor patterns in gut virome and bacterial community composition distinguish pediatric IBD patients from healthy controls. Probiotics are associated with bacterial microbiota composition. These exploratory results need confirmation in larger studies.

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          Pathogenesis of Inflammatory Bowel Disease and Recent Advances in Biologic Therapies

          Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder with an unknown etiology. IBD is composed of two different disease entities: Crohn's disease (CD) and ulcerative colitis (UC). IBD has been thought to be idiopathic but has two main attributable causes that include genetic and environmental factors. The gastrointestinal tract in which this disease occurs is central to the immune system, and the innate and the adaptive immune systems are balanced in complex interactions with intestinal microbes under homeostatic conditions. However, in IBD, this homeostasis is disrupted and uncontrolled intestinal inflammation is perpetuated. Recently, the pathogenesis of IBD has become better understood owing to advances in genetic and immunologic technology. Moreover, new therapeutic strategies are now being implemented that accurately target the pathogenesis of IBD. Beyond conventional immunesuppressive therapy, the development of biological agents that target specific disease mechanisms has resulted in more frequent and deeper remission in IBD patients, with mucosal healing as a treatment goal of therapy. Future novel biologics should overcome the limitations of current therapies and ensure that individual patients can be treated with optimal drugs that are safe and precisely target IBD.
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            The virome in host health and disease.

            The mammalian virome includes diverse commensal and pathogenic viruses that evoke a broad range of immune responses from the host. Sustained viral immunomodulation is implicated in a variety of inflammatory diseases, but also confers unexpected benefits to the host. These outcomes of viral infections are often dependent on host genotype. Moreover, it is becoming clear that the virome is part of a dynamic network of microorganisms that inhabit the body. Therefore, viruses can be viewed as a component of the microbiome, and interactions with commensal bacteria and other microbial agents influence their behavior. This piece is a review of our current understanding of how the virome, together with other components of the microbiome, affects the function of the host immune system to regulate health and disease.
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              The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions.

              We discuss the tripartite pathophysiological circuit of inflammatory bowel disease (IBD), involving the intestinal microbiota, barrier function, and immune system. Dysfunction in each of these physiological components (dysbiosis, leaky gut, and inflammation) contributes in a mutually interdependent manner to IBD onset and exacerbation. Genetic and environmental risk factors lead to disruption of gut homeostasis: genetic risks predominantly affect the immune system, environmental risks predominantly affect the microbiota, and both affect barrier function. Multiple genetic and environmental 'hits' are likely necessary to establish and exacerbate disease. Most conventional IBD therapies currently target only one component of the pathophysiological circuit, inflammation; however, many patients with IBD do not respond to immune-modulating therapies. Hope lies in new classes of therapies that target the microbiota and barrier function.
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                Author and article information

                Journal
                Journal of Pediatric Gastroenterology and Nutrition
                Journal of Pediatric Gastroenterology and Nutrition
                Ovid Technologies (Wolters Kluwer Health)
                0277-2116
                2019
                January 2019
                : 68
                : 1
                : 30-36
                Article
                10.1097/MPG.0000000000002140
                6310095
                30169455
                b8fb34b3-3657-44e2-b535-17870c71ea49
                © 2019
                History

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