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 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 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.

scholarly journals Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 780 ◽  
Author(s):  
Jan Bilski ◽  
Agnieszka Mazur-Bialy ◽  
Dagmara Wojcik ◽  
Marcin Surmiak ◽  
Marcin Magierowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Special Role ◽  
Mesenteric Adipose Tissue ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBDs) are a group of disorders which include ulcerative colitis and Crohn’s disease. Obesity is becoming increasingly more common among patients with inflammatory bowel disease and plays a role in the development and course of the disease. This is especially true in the case of Crohn’s disease. The recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue, also known as “creeping fat”, in pathomechanism, leading to intestinal inflammation. The involvement of altered adipocyte function and the deregulated production of adipokines, such as leptin and adiponectin, has been suggested in pathogenesis of IBD. In this review, we discuss the epidemiology and pathophysiology of obesity in IBD, the influence of a Western diet on the course of Crohn’s disease and colitis in IBD patients and animal’s models, and the potential role of adipokines in these disorders. Since altered body composition, decrease of skeletal muscle mass, and development of pathologically changed mesenteric white adipose tissue are well-known features of IBD and especially of Crohn’s disease, we discuss the possible crosstalk between adipokines and myokines released from skeletal muscle during exercise with moderate or forced intensity. The emerging role of microbiota and the antioxidative and anti-inflammatory enzymes such as intestinal alkaline phosphatase is also discussed, in order to open new avenues for the therapy against intestinal perturbations associated with IBD.

scholarly journals Medical management of Crohn’s disease: state of the art and future perspectives

2019 ◽  
Vol 13 (3) ◽  
pp. 152-160
Author(s):  
Fabio Salvatore Macaluso
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Molecular Mechanisms ◽  
Oral Route ◽  
New Drugs ◽  
Mediators Of Inflammation ◽  
Bowel Diseases ◽  
Intrinsic Complexity ◽  
Inflammatory Bowel

Over the past decade, the improvement in the understanding of the molecular mechanisms of Crohn’s disease (CD) led to the development of more targeted therapies, including biologics - i.e. monoclonal antibodies that selectively block key mediators of inflammation - and novel small molecule drugs - i.e. compounds with a molecular weight <1 kDa able to diffuse through cell membranes and then fit for the oral route of administration - which will enrich the therapeutic armamentarium of CD soon. In parallel with the expansion of the medical options, the therapeutic targets to be achieved in patients with CD have changed. In particular, we moved from the simple control of symptoms to more ambitious goals which aim to permanently extinguish the inflammation, even the subclinical one. As a consequence, the role of some of the conventional drugs which have been used in CD for several years, such as 5-aminosalicylates and conventional immunosuppressants, is becoming more limited in favor of these new drugs. This profound modification of CD therapy and the intrinsic complexity of the disease are relevant to the point that the management of inflammatory bowel diseases is gradually becoming a subspecialty in the field of gastroenterology or internal medicine.

scholarly journals The Possible Pathogenic Role of IgG4-Producing Plasmablasts in Stricturing Crohn’s Disease

Pathobiology ◽  
2022 ◽  
pp. 1-11
Author(s):  
Omar Bushara ◽  
David Joseph Escobar ◽  
Samuel Edward Weinberg ◽  
Leyu Sun ◽  
Jie Liao ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Adaptive Immune Response ◽  
Stricture Formation ◽  
Tfh Cells ◽  
Follicular Helper ◽  
The Us ◽  
Inflammatory Bowel

<b><i>Background:</i></b> Crohn’s disease (CD) is a condition on the spectrum of inflammatory bowel disease that affects up to 20 people per 100,000 in the US annually, and with incidence increasing. One of the most significant sources of morbidity in CD is the formation of strictures, with resultant intestinal blockage a common indication for hospitalization and surgical intervention in these patients. The pathophysiology of stricture formation is not fully understood. However, the fibroplasia that leads to fibrostenotic stricture formation may have shared pathophysiology with IgG4-related fibrosis. <b><i>Summary:</i></b> Initial intestinal inflammation recruits innate immune cells, such as neutrophils, that secrete IL-1β and IL-23, which induces a type 17 CD4+ T-helper T-cell (Th17)-mediated adaptive immune response. These CD4+ Th17 T cells also contribute to inflammation by secreting proinflammatory cytokines such as IL-17 and IL-21. IL-21 recruits and stimulates CD4+ T follicular helper (Tfh) cells, which secrete more IL-21. This causes ectopic germinal center formation, recruiting and stimulating naïve B cells. The IL-17 and IL-21 produced by Th17 cells and Tfh cells also induce IgG4 plasmablast differentiation. Finally, these IgG4-producing plasmablasts secrete platelet-derived growth factor (PDGF), which activates local PDGF-receptor expressing fibroblasts and myofibroblasts, resulting in uncontrolled fibroplasia.

scholarly journals Dietary Strategies for Maintenance of Clinical Remission in Inflammatory Bowel Diseases: Are We There Yet?

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2018 ◽  
Author(s):  
Konstantinos Gkikas ◽  
Konstantinos Gerasimidis ◽  
Simon Milling ◽  
Umer Z. Ijaz ◽  
Richard Hansen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Future Research ◽  
Clinical Relapse ◽  
Exclusive Enteral Nutrition ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Dietary Strategies

The etiopathogenesis of Inflammatory bowel disease (IBD) is a result of a complex interaction between host immune response, the gut microbiome and environmental factors, such as diet. Although scientific advances, with the use of biological medications, have revolutionized IBD treatment, the challenge for maintaining clinical remission and delaying clinical relapse is still present. As exclusive enteral nutrition has become a well-established treatment for the induction of remission in pediatric Crohn’s disease, the scientific interest regarding diet in IBD is now focused on the development of follow-on dietary strategies, which aim to suppress colonic inflammation and delay a disease flare. The objective of this review is to present an extensive overview of the dietary strategies, which have been used in the literature to maintain clinical remission in both Crohn’s disease and Ulcerative colitis, and the evidence surrounding the association of dietary components with clinical relapse. We also aim to provide study-related recommendations to be encompassed in future research studies aiming to investigate the role of diet during remission periods in IBD.

Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

1988 ◽  
Vol 27 (03) ◽  
pp. 83-86 ◽  
Author(s):  
B. Briele ◽  
F. Wolf ◽  
H. J. Biersack ◽  
F. F. Knapp ◽  
A. Hotze
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Cell Uptake ◽  
Disease Extent ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

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 Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Bruno Rafael Ramos de Mattos ◽  
Maellin Pereira Gracindo Garcia ◽  
Julia Bier Nogueira ◽  
Lisiery Negrini Paiatto ◽  
Cassia Galdino Albuquerque ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Severe Disease ◽  
Biological Therapies ◽  
Promising Alternative ◽  
Biological Treatments ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
And Behavior

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

Quality of Life Considering Patients with Chronic Inflammatory Bowel Diseases - Natural and Parenteral Nutrition

2014 ◽  
Vol 86 (9) ◽  
Author(s):  
Aneta Raczkowska ◽  
Michał Ławiński ◽  
Aleksandra Gradowska ◽  
Urszula Zielińska-Borkowska
Keyword(s):  
Quality Of Life ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Parenteral Nutrition ◽  
Inflammatory Bowel Diseases ◽  
Nutritional Therapy ◽  
Bowel Diseases ◽  
Inflammatory Bowel

AbstractOne of the elements of treatment considering inflammatory bowel diseases is nutritional therapy. The duration of the above-mentioned depends on the prevalence of such symptoms as fever, bowel move-ments, length of the functioning gastrointestinal tract, stoma and intestinal fistula presence. Nutritional therapy is an essential element of successful treatment alongside pharmacological, surgical, and biological therapy, as well as other methods. Crohn's disease and ulcerative colitis considered as chronic diseases, lead towards physical and biopsychosocial disability, being responsible for the reduction in the quality of life.was to determine the quality of life after surgical procedures in case of patients diagnosed with Crohn's disease and ulcerative colitis, subjected to natural and parenteral nutrition.The study group comprised 52 patients from the Department of Gastroen-terology, Military Medical Institute, and Department of Surgery and Clinical Nutrition, Clinical Hospital in Warsaw. The study was performed between October, 2011 and April, 2012. The World Health Organization Quality of Life Instrument - Bref (WHOQOL-BREF) questionnaire was used to deter-mine the patients’ quality of life.A lower quality of life was observed in case of patients subjected to parenteral nutrition, poor education, disease symptoms exacerbation, in the majority-rural inhabitants. The quality of life does not depend on gender, type of disease, family status, and additional medical care.

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