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      Inflammatory bowel disease and immunonutrition: novel therapeutic approaches through modulation of diet and the gut microbiome

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          Summary

          Inflammatory bowel disease ( IBD) is a chronic inflammatory condition of the gastrointestinal tract, thought to at least in part reflect an aberrant immune response to gut bacteria. IBD is increasing in incidence, particularly in populations that have recently immigrated to western countries. This suggests that environmental factors are involved in its pathogenesis. We hypothesize that the increase in IBD rates might reflect the consumption of an unhealthy Western diet, containing excess calories and lacking in key nutritional factors, such as fibre and vitamin D. Several recent studies have determined that dietary factors can dramatically influence the activation of immune cells and the mediators they release through a process called immunonutrition. Moreover, dietary changes can profoundly affect the balance of beneficial versus pathogenic bacteria in the gut. This microbial imbalance can alter levels of microbiota‐derived metabolites that in turn can influence innate and adaptive intestinal immune responses. If the diet–gut microbiome disease axis does indeed underpin much of the ‘western’ influence on the onset and progression of IBD, then tremendous opportunity exists for therapeutic changes in lifestyle, to modulate the gut microbiome and to correct immune imbalances in individuals with IBD. This review highlights four such therapeutic strategies – probiotics, prebiotics, vitamin D and caloric restriction – that have the potential to improve and add to current IBD treatment regimens.

          Most cited references107

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          Adapting to obesity with adipose tissue inflammation

          Adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Here, Reilly and Saltiel review the cellular and molecular mechanisms of obesity-induced inflammation in adipose tissue and discuss potential therapeutic approaches.
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            Meta-analyses of human gut microbes associated with obesity and IBD.

            Recent studies have linked human gut microbes to obesity and inflammatory bowel disease, but consistent signals have been difficult to identify. Here we test for indicator taxa and general features of the microbiota that are generally consistent across studies of obesity and of IBD, focusing on studies involving high-throughput sequencing of the 16S rRNA gene (which we could process using a common computational pipeline). We find that IBD has a consistent signature across studies and allows high classification accuracy of IBD from non-IBD subjects, but that although subjects can be classified as lean or obese within each individual study with statistically significant accuracy, consistent with the ability of the microbiota to experimentally transfer this phenotype, signatures of obesity are not consistent between studies even when the data are analyzed with consistent methods. The results suggest that correlations between microbes and clinical conditions with different effect sizes (e.g. the large effect size of IBD versus the small effect size of obesity) may require different cohort selection and analysis strategies.
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              Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis.

              Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor (TNF)-α. Its efficacy as maintenance therapy for patients with ulcerative colitis has not been studied in a controlled, double-blind trial. Ulcerative colitis long-term remission and maintenance with adalimumab 2 (ULTRA 2) was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of adalimumab in induction and maintenance of clinical remission in 494 patients with moderate-to-severe ulcerative colitis who received concurrent treatment with oral corticosteroids or immunosuppressants. Patients were stratified based on prior exposure to TNF-α antagonists (either had or had not been previously treated with anti-TNF-α) and randomly assigned to groups given adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg every other week or placebo. Primary end points were remission at weeks 8 and 52. Overall rates of clinical remission at week 8 were 16.5% on adalimumab and 9.3% on placebo (P = .019); corresponding values for week 52 were 17.3% and 8.5% (P = .004). Among anti-TNF-α naïve patients, rates of remission at week 8 were 21.3% on adalimumab and 11% on placebo (P = .017); corresponding values for week 52 were 22% and 12.4% (P = .029). Among patients who had previously received anti-TNF agents, rates of remission at week 8 were 9.2% on adalimumab and 6.9% on placebo (P = .559); corresponding values for week 52 were 10.2% and 3% (P = .039). Serious adverse events occurred in 12% of patients given adalimumab or placebo. Serious infections developed in 1.6% of patients given adalimumab and 1.9% given placebo. In the group given adalimumab, 1 patient developed squamous cell carcinoma and 1 developed gastric cancer. Adalimumab was safe and more effective than placebo in inducing and maintaining clinical remission in patients with moderate-to-severe ulcerative colitis who did not have an adequate response to conventional therapy with steroids or immunosuppressants. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                laurasly@mail.ubc.ca
                bvallance@cw.bc.ca
                Journal
                Immunology
                Immunology
                10.1111/(ISSN)1365-2567
                IMM
                Immunology
                John Wiley and Sons Inc. (Hoboken )
                0019-2805
                1365-2567
                16 May 2018
                September 2018
                : 155
                : 1 ( doiID: 10.1111/imm.2018.155.issue-1 )
                : 36-52
                Affiliations
                [ 1 ] Department of Paediatrics BC Children's Hospital University of British Columbia Vancouver BC Canada
                Author notes
                [*] [* ] Correspondence: Dr Bruce A. Vallance, Department of Paediatrics, Division of Gastroenterology, University of British Columbia and BC Children's Hospital, CH.I.L.D. Foundation Chair in Paediatric Gastroenterology, Rm. K4‐188, 4480 Oak Street Vancouver, BC V6H 3V4, Canada. Email: bvallance@ 123456cw.bc.ca

                or

                Dr Laura M. Sly, Department of Paediatrics, Division of Gastroenterology, University of British Columbia and BC Children's Hospital, Rm. A5‐142, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada. Email: laurasly@ 123456mail.ubc.ca

                Senior author: Bruce A. Vallance

                [†]

                These authors contributed equally.

                Author information
                http://orcid.org/0000-0001-9057-9041
                Article
                PMC6099178 PMC6099178 6099178 IMM12939
                10.1111/imm.12939
                6099178
                29693729
                dae5ccce-62ea-443d-8e91-8aa646866371
                © 2018 John Wiley & Sons Ltd
                History
                : 13 February 2018
                : 28 March 2018
                : 18 April 2018
                Page count
                Figures: 2, Tables: 2, Pages: 17, Words: 14162
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                imm12939
                September 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.4 mode:remove_FC converted:20.08.2018

                prebiotics,microbiome,probiotics,vitamin D,gut,fasting,immunonutrition

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