Are Immunosuppressants Becoming Obsolete?

2016 ◽  
Vol 34 (Suppl. 1) ◽  
pp. 56-60 ◽  
Author(s):  
Donata Lissner ◽  
Britta Siegmund
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Therapeutic Option ◽  
Significant Drop ◽  
Current Role ◽  
Early Introduction ◽  
Inflammatory Bowel ◽  
Maintenance Of Remission ◽  
Therapy Of Crohn's Disease

Historically, in the 1950s, the introduction of simple, old-fashioned steroids resulted in a significant drop in mortality and hence offered for the first time a real therapeutic option for patients with inflammatory bowel disease. However, as we are all aware of, steroids are no option for maintenance of remission. This review will provide an overview of the available data on the current role of azathioprine in the therapy of Crohn's disease. Based on several controlled trials, the place of azathioprine for maintenance of remission is indisputable. Data from a pediatric cohort suggested that early introduction of azathioprine is beneficial for the disease course. Two recent studies aimed at reproducing these data in adult populations and failed. Hence indicating that azathioprine should only be introduced for maintenance of remission in a step-up-wise approach. An additional role for azathioprine in combo therapy with TNF antibodies has been indicated by several trials revealing a substantial benefit on response. This is partly attributed to the gain in the therapeutic effect by azathioprine itself and possibly through reduction of anti-drug antibody development. In summary, the current role of azathioprine in the therapy of Crohn's disease is manifold and still has an impact in times of targeted therapy.

scholarly journals The role of epigenetic modifications for the pathogenesis of Crohn's disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
M. Hornschuh ◽  
E. Wirthgen ◽  
M. Wolfien ◽  
K. P. Singh ◽  
O. Wolkenhauer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Biomarkers ◽  
Insight Into ◽  
Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

scholarly journals Role of Probiotics and Their Metabolites in Inflammatory Bowel Diseases (IBDs)

2021 ◽  
Vol 12 (1) ◽  
pp. 56-66
Author(s):  
Toumi Ryma ◽  
Arezki Samer ◽  
Imene Soufli ◽  
Hayet Rafa ◽  
Chafia Touil-Boukoffa
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
Short Chain Fatty Acids ◽  
Active Metabolites ◽  
Complex Disorders ◽  
Inflammatory Bowel

Inflammatory Bowel Disease (IBD) is a term used to describe a group of complex disorders of the gastrointestinal (GI) tract. IBDs include two main forms: Crohn’s Disease (CD) and Ulcerative Colitis (UC), which share similar clinical symptoms but differ in the anatomical distribution of the inflammatory lesions. The etiology of IBDs is undetermined. Several hypotheses suggest that Crohn’s Disease and Ulcerative Colitis result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. While there is no cure for IBDs, most common treatments (medication and surgery) aim to reduce inflammation and help patients to achieve remission. There is growing evidence and focus on the prophylactic and therapeutic potential of probiotics in IBDs. Probiotics are live microorganisms that regulate the mucosal immune system, the gut microbiota and the production of active metabolites such as Short-Chain Fatty Acids (SCFAs). This review will focus on the role of intestinal dysbiosis in the immunopathogenesis of IBDs and understanding the health-promoting effects of probiotics and their metabolites.

scholarly journals Therapeutic role of methotrexate in pediatric Crohn’s disease

2018 ◽  
Vol 18 (3) ◽  
pp. 211-216
Author(s):  
Zlatko Djurić ◽  
Ljiljana Šaranac ◽  
Ivana Budić ◽  
Voja Pavlović ◽  
Jelena Djordjević
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Normal Growth ◽  
Mucosal Healing ◽  
Main Role ◽  
Therapeutic Role ◽  
Hepatosplenic T Cell Lymphoma ◽  
Maintenance Of Remission

The main role of therapy in Crohn’s disease (CD) is to achieve long-term clinical remission, and to allow for normal growth and development of children. The immunomodulatory drugs used for the maintenance of remission in CD include thiopurines (azathioprine and 6-mercaptopurine) and methotrexate (MTX). Development of hepatosplenic T-cell lymphoma in some patients with inflammatory bowel disease, treated with thiopurines only or in combination with anti-tumor necrosis factor agents, resulted in a growing interest in the therapeutic application of MTX in children suffering from CD. This review summarizes the literature on the therapeutic role of MTX in children with CD. MTX is often administered as a second-line immunomodulator, and 1-year clinical remission was reported in 25–69% of children with CD after excluding for the use of thiopurines. Initial data on MTX effectiveness in mucosal healing, and as a first-line immunomodulator in pediatric patients with CD, are promising. A definite conclusion, however, may only be made on the basis of additional research with a larger number of subjects.

scholarly journals Characterization of fungal and bacterial dysbiosis in young adult Chinese patients with Crohn’s disease

2020 ◽  
Vol 13 ◽  
pp. 175628482097120
Author(s):  
Xinyun Qiu ◽  
Xiaojing Zhao ◽  
Xiufang Cui ◽  
Xiaqiong Mao ◽  
Nana Tang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Chinese Patients ◽  
Bacterial Composition ◽  
Structural Differences ◽  
Inflammatory Bowel ◽  
Fungal Microbiome ◽  
Chinese Subjects

Intestinal microbiota dysbiosis has been described in inflammatory bowel disease (IBD), but data from China are limited. In this study, we performed molecular analysis of the fecal microbial community from 20 healthy Chinese subjects and 25 patients with Crohn’s disease (CD), and evaluated associations with bacterial and fungal compositions. Decreased richness and diversity of bacterial composition was observed in the CD group compared with healthy (H) subjects. Significant structural differences in bacterial (but not fungal) composition among healthy controls and CD patients were found. A reduction in Firmicutes and Actinobacteria abundance, and overrepresentation of Proteobacteria were observed in the CD patients compared with the H group. The Escherichia-Shigella genus was overrepresented in the CD group, whereas Faecalibacterium, Gemmiger, Bifidobacterium, Romboutsia, Ruminococcus, Roseburia, and Fusicatenibacter abundance were decreased in the CD group compared with H subjects. Differences in fungal microbiota between the H and CD groups were observed at the genus rather than at the phylum level. The Candida genus was overrepresented in the CD (active disease) group compared with the H group, whereas no difference between CD (remission) and H groups was observed. Aspergillus, unclassified_Sordariomycetes, and Penicillium genera had greater representation in the H subjects compared with the CD group. Bacterial and fungal intra- and inter-kingdom correlations were observed between the H and CD groups. Therefore, fecal bacterial and fungal microbiome communities differed considerably between H and CD patients, and between Chinese and Western populations. The role of gut microbiota in homeostasis and in gastrointestinal disorders should be investigated further.

Differential relationships of somatization, depression, and anxiety to severity of Crohn’s disease

2020 ◽  
pp. 135910532090987 ◽  
Author(s):  
Shirley Regev ◽  
Shmuel Odes ◽  
Vered Slonim-Nevo ◽  
Michael Friger ◽  
Doron Schwartz ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Structural Equation ◽  
Equation Modeling ◽  
Relative Role ◽  
Depression And Anxiety ◽  
Inflammatory Bowel ◽  
Unique Predictor

Patients with Crohn’s disease, an inflammatory bowel disease, struggle with chronic somatic symptoms that could bring about emotional distress. This study assessed the relative role of somatization, and depressive and anxiety symptoms in disease activity among 619 Crohn’s patients (18–79 years; 58.3% women). Structural equation modeling revealed that somatization was the only unique predictor of disease activity beyond depression and anxiety. In addition, the effect of somatization on disease activity was stronger in men compared to women. Findings suggest that somatization represents a distinct domain of psychological distress that may play a role in the health of patients with Crohn’s disease.

scholarly journals Comorbid Inflammatory Diseases of Digestive System and Eye

2021 ◽  
Vol 18 (1) ◽  
pp. 20-29
Author(s):  
S. A. Bulgakov ◽  
G. M. Chernakova ◽  
E. A. Kleshcheva ◽  
S. V. Simonova
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Ophthalmological Examination ◽  
Extraintestinal Manifestations ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases, which are often accompanied by inflammation of other organs. This article presents modern data on etiology, pathogenesis and clinical course of inflammatory bowel diseases, as well as information on extraintestinal eye manifestations of nonspecific ulcerative colitis and Crohn’s disease. The role of microbiota, genetic factors, immune system defects in pathogenesis of intestinal inflammation and extraintestinal eye manifestations is considered. The possibility the development of ophthalmopathology not only against the background of intestinal inflammation, but also as a consequence of therapeutic and surgical methods of treatment of ulcerative colitis and Crohn’s disease is noted. The peculiarities of the course of episcleritis/scleritis, keratitis, uveitis, chorioretinitis, optical neuritis for patients with inflammatory bowel diseases are considered. The presence of these complications may reflect the activity of the underlying disease, which in some cases requires correction of therapy. Anterior uveitis and episcleritis/scleritis are the most common extraintestinal manifestations of inflammatory bowel disease. Inflammation of tissues of the posterior segment of the eye and optic nerve against the background of ulcerative colitis and Crohn’s disease are less common, but are of clinical importance, as they can catastrophically damage the structures of the eye and, as a consequence, lead to complete blindness. Considering the possibility of mild clinical symptoms and asymptomatic course of inflammation in the eye envelopes, the importance of ophthalmological examination of all patients with ulcerative colitis and Crohn’s disease is emphasized. Aspects of modern therapy of ophthalmopathology and background intestinal inflammation are highlighted. Biological preparations — antagonists of pro-inflammatory cytokines — have been identified as the most promising in the treatment of inflammatory intestinal diseases and extraintestinal manifestations. The important role of proper nutrition and biologically active supplements containing omega-3 fatty acids, vitamin D, microelements, was noted as auxiliary therapy of both intestinal and extraintestinal inflammation.

scholarly journals Crohn’s Disease Remission with a Plant-Based Diet: A Case Report

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1385 ◽  
Author(s):  
Kelsea Sandefur ◽  
Hana Kahleova ◽  
Alan N. Desmond ◽  
Eden Elfrink ◽  
Neal D. Barnard
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Chronic Inflammatory Bowel Disease ◽  
Standard Medical Therapy ◽  
Westernized Diet ◽  
Inflammatory Bowel ◽  
Maintenance Of Remission ◽  
Vegetables And Fruits ◽  
Diet And Lifestyle

Crohn’s disease (CD) is a form of chronic inflammatory bowel disease (IBD). The etiology of CD is thought to be multi-factorial; genetic factors, dietary and environmental exposures, immune events, and dysfunction of the gut microbiome are all though to play a role. The prevalence of CD is increasing globally and is higher in countries with a Westernized diet and lifestyle. Several human trials have demonstrated that plant-based dietary therapies may have utility in both the treatment of acute CD flares and the maintenance of remission. This case study describes a young adult male with newly diagnosed CD who failed to enter clinical remission despite standard medical therapy. After switching to a diet based exclusively on grains, legumes, vegetables, and fruits, he entered clinical remission without need for medication and showed no signs of CD on follow-up colonoscopy.

scholarly journals Treatment of Inflammatory Bowel Disease in Children

1990 ◽  
Vol 4 (7) ◽  
pp. 404-406 ◽  
Author(s):  
D Grant Gall
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Bowel Disease ◽  
Growth Failure ◽  
Nutritional Therapy ◽  
Inflammatory Bowel

As no curative therapy exists, supportive measures play an important role in the management of patients with inflammatory bowel disease (IBO). Aminosalicylic acid (ASA) compounds and corticosteroids remain the mainstay of medical therapy. Aminosalicylates are recommended for therapy of mild to moderate active ulcerative colitis and for the maintenance of remission in ulcerative colitis. The role of 5-ASA preparations in Crohn's disease is less clear. In granulomatous colitis, 5-ASA therapy is recommended. With the development of new delivery systems, the role for 5-ASA in the treatment of small bowel Crohn's disease is under investigation. Prednisone remains the drug of choice in severe ulcerative colitis and active Crohn's disease. The role of immunosuppressive drugs in pediatric patients is unclear. Nutritional therapy has been an important advance in the treatment of children with Crohn's disease, especially those with growth failure. Nutritional therapy can consist of combined total parenteral and enteral nutrition or enteral nutrition alone. An initial period of total parenteral nutrition followed by a six to eight week course of enteral therapy with a semisynthetic diet has been shown to be effective in the management of patients with severe active disease and growth failure.

scholarly journals Cyclosporine and inflammatory bowel disease: buying time

1998 ◽  
Vol 7 (3) ◽  
pp. 145-147 ◽  
Author(s):  
M. A. C. Meijssen
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Therapeutic Option ◽  
Short Term ◽  
Disease Remission ◽  
Acute Exacerbations ◽  
Inflammatory Bowel

Cyclosporine is an effective drug in acute exacerbations of corticosteroid resistant ulcerative colitis, but its efficacy to maintain disease remission is not clear. Cyclosporine may not be as effective in Crohn's disease. However, being a rapidly acting immunosuppressant, cyclosporine may be a valuable therapeutic option in the short-term to treat corticosteroid resistant Crohn's disease and ulcerative colitis.

scholarly journals Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

2019 ◽  
Vol 116 (52) ◽  
pp. 26717-26726 ◽  
Author(s):  
Paola Menghini ◽  
Daniele Corridoni ◽  
Ludovica F. Buttó ◽  
Abdullah Osme ◽  
Sushma Shivaswamy ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Intestinal Microbiome ◽  
Lactobacillus Salivarius ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Antiinflammatory Effects

Crohn’s disease and ulcerative colitis are chronic and progressive inflammatory bowel diseases (IBDs) that are attributed to dysregulated interactions between the gut microbiome and the intestinal mucosa-associated immune system. There are limited studies investigating the role of either IL-1α or IL-1β in mouse models of colitis, and no clinical trials blocking either IL-1 have yet to be performed. In the present study, we show that neutralization of IL-1α by a specific monoclonal antibody against murine IL-1α was highly effective in reducing inflammation and damage in SAMP mice, mice that spontaneously develop a Crohn’s-like ileitis. Anti-mouse IL-1α significantly ameliorated the established, chronic ileitis and also protected mice from developing acute DSS-induced colitis. Both were associated with taxonomic divergence of the fecal gut microbiome, which was treatment-specific and not dependent on inflammation. Anti–IL-1α administration led to a decreased ratio ofProteobacteriatoBacteroidetes, decreased presence ofHelicobacterspecies, and elevated representation ofMucispirillum schaedleriandLactobacillus salivarius. Such modification in flora was functionally linked to the antiinflammatory effects of IL-1α neutralization, as blockade of IL-1α was not effective in germfree SAMP mice. Furthermore, preemptive dexamethasone treatment of DSS-challenged SAMP mice led to changes in flora composition without preventing the development of colitis. Thus, neutralization of IL-1α changes specific bacterial species of the intestinal microbiome, which is linked to its antiinflammatory effects. These functional findings may be of significant value for patients with IBD, who may benefit from targeted IL-1α–based therapies.

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