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      The Role of Vitamin D in Inflammatory Bowel Disease: Mechanism to Management

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          Abstract

          Vitamin D has been linked to human health benefits that extend far beyond its established actions on calcium homeostasis and bone metabolism. One of the most well studied facets of extra-skeletal vitamin D is its activity as an immuno-modulator, in particular its potent anti-inflammatory effects. As a consequence, vitamin D deficiency has been associated with inflammatory diseases including inflammatory bowel disease (IBD). Low serum levels of the major circulating form of vitamin D, 25-hydroxyvitamin D (25-OH-D) are significantly more prevalent in patients with IBD, particularly in the winter and spring months when UV-induced synthesis of vitamin D is lower. Dietary malabsorption of vitamin D may also contribute to low serum 25(OH)D in IBD. The benefits of supplementation with vitamin D for IBD patients are still unclear, and improved vitamin D status may help to prevent the onset of IBD as well as ameliorating disease severity. Beneficial effects of vitamin D in IBD are supported by pre-clinical studies, notably with mouse models, where the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D) has been shown to regulate gastrointestinal microbiota function, and promote anti-inflammatory, tolerogenic immune responses. The current narrative review aims to summarise the different strands of data linking vitamin D and IBD, whilst also outlining the possible beneficial effects of vitamin D supplementation in managing IBD in humans.

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          Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

          Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.
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            ACG Clinical Guideline

            Ulcerative colitis (UC) is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the evidence was not appropriate for GRADE, but there was consensus of significant clinical merit, "key concept" statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
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              ACG Clinical Guideline: Management of Crohn’s Disease in Adults

              Crohn's disease is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of Crohn's disease has steadily increased over the past several decades. The diagnosis and treatment of patients with Crohn's disease has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with Crohn's disease. These guidelines are established for clinical practice with the intent of suggesting preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When exercising clinical judgment, health-care providers should incorporate this guideline along with patient's needs, desires, and their values in order to fully and appropriately care for patients with Crohn's disease. This guideline is intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. To evaluate the level of evidence and strength of recommendations, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                07 May 2019
                May 2019
                : 11
                : 5
                : 1019
                Affiliations
                [1 ]Nutrition Nurses, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TH 1, UK
                [2 ]Gastroenterology Department, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB 2, UK; sheldon.cooper@ 123456uhb.nhs.uk
                [3 ]NIHR Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TH, UK; s.ghosh@ 123456bham.ac.uk
                [4 ]Institute of Translational Medicine, University of Birmingham, Birmingham B15 2TH, UK
                [5 ]Institute of Metabolism and Systems Research, The University of Birmingham, Birmingham B15 2TT, UK; m.hewison@ 123456bham.ac.uk
                Author notes
                [* ]Correspondence: jane.fletcher@ 123456uhb.nhs.uk ; Tel.: +44-121-371-4561
                Author information
                https://orcid.org/0000-0001-5033-8278
                https://orcid.org/0000-0001-5806-9690
                Article
                nutrients-11-01019
                10.3390/nu11051019
                6566188
                31067701
                065d6871-526f-43f2-b6b3-81634702093f
                © 2019 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 (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 April 2019
                : 29 April 2019
                Categories
                Review

                Nutrition & Dietetics
                vitamin d,ibd,crohn’s disease,ulcerative colitis,supplementation,deficiency
                Nutrition & Dietetics
                vitamin d, ibd, crohn’s disease, ulcerative colitis, supplementation, deficiency

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