Neurologic manifestations in inflammatory bowel diseases: Current knowledge and novel insights

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

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Epigenetics of Inflammatory Bowel Disease: Unraveling Pathogenic Events

Crohn's & Colitis 360 ◽

10.1093/crocol/otz017 ◽

2019 ◽

Vol 1 (2) ◽

Cited By ~ 2

Author(s):

Beatriz Mateos ◽

Cora Palanca-Ballester ◽

Esteban Saez-Gonzalez ◽

Inés Moret ◽

Adrian Lopez ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Practice ◽

Inflammatory Bowel Diseases ◽

Drug Response ◽

Current Knowledge ◽

Epigenetic Biomarkers ◽

Bowel Diseases ◽

Potential Applicability ◽

Inflammatory Bowel ◽

New Biomarkers

Abstract Epigenetics has emerged as a new and promising field in recent years. Because there exists a need to find new biomarkers and improve diagnosis, prognosis, and drug response for inflammatory bowel diseases, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to the clinical practice. In this review, we present an overview of the current knowledge and its potential applicability of this emerging field in inflammatory bowel diseases.

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Evidence for a Potential Role of Metallothioneins in Inflammatory Bowel Diseases

Mediators of Inflammation ◽

10.1155/2009/729172 ◽

2009 ◽

Vol 2009 ◽

pp. 1-9 ◽

Cited By ~ 23

Author(s):

Anouk Waeytens ◽

Martine De Vos ◽

Debby Laukens

Keyword(s):

Inflammatory Bowel Diseases ◽

Potential Role ◽

Current Knowledge ◽

Zinc Homeostasis ◽

Central Position ◽

Small Proteins ◽

Immune Mediated ◽

Bowel Diseases ◽

Inflammatory Bowel

Inflammatory bowel diseases (IBDs) are a group of chronic, relapsing, immune-mediated disorders of the intestine, including Crohn's disease and ulcerative colitis. Recent studies underscore the importance of the damaged epithelial barrier and the dysregulated innate immune system in their pathogenesis. Metallothioneins (MTs) are a family of small proteins with a high and conserved cysteine content that are rapidly upregulated in response to an inflammatory stimulus. Herein, we review the current knowledge regarding the expression and potential role of MTs in IBD. MTs exert a central position in zinc homeostasis, modulate the activation of the transcription factor nuclear factor (NF)-B, and serve as antioxidants. In addition, MTs could be involved in IBD through their antiapoptotic effects or through specific immunomodulating extracellular effects. Reports on MT expression in IBD are contradictory but clearly demonstrate a deviant MT expression supporting the idea that these aberrations in IBD require further clarification.

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Environment and the Inflammatory Bowel Diseases

Canadian Journal of Gastroenterology ◽

10.1155/2013/102859 ◽

2013 ◽

Vol 27 (3) ◽

pp. e18-e24 ◽

Cited By ~ 70

Author(s):

Alexandra Frolkis ◽

Levinus A Dieleman ◽

Herman W Barkema ◽

Remo Panaccione ◽

Subrata Ghosh ◽

...

Keyword(s):

Risk Factors ◽

Environmental Factors ◽

Environmental Risk ◽

Inflammatory Bowel Diseases ◽

Current Knowledge ◽

Environmental Risk Factors ◽

Past Century ◽

Commensal Flora ◽

Bowel Diseases ◽

Inflammatory Bowel

Inflammatory bowel diseases (IBD), which consists of Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gas-trointestinal tract. In genetically susceptible individuals, the interaction between environmental factors and normal intestinal commensal flora is believed to lead to an inappropriate immune response that results in chronic inflammation. The incidence of IBD have increased in the past century in developed and developing countries. The purpose of the present review is to summarize the current knowledge of the association between environmental risk factors and IBD. A number of environmental risk factors were investigated including smoking, hygiene, microorganisms, oral contraceptives, antibiotics, diet, breast-feeding, geographical factors, pollution and stress. Inconsistent findings among the studies highlight the complex pathogenesis of IBD. Additional studies are necessary to identify and elucidate the role of environmental factors in IBD etiology.

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Emerging Role of Exosomes in Diagnosis and Treatment of Infectious and Inflammatory Bowel Diseases

Cells ◽

10.3390/cells9051111 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1111 ◽

Cited By ~ 4

Author(s):

Anaïs Larabi ◽

Nicolas Barnich ◽

Hang Thi Thu Nguyen

Keyword(s):

Inflammatory Bowel Diseases ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Intestinal Inflammation ◽

Current Knowledge ◽

Biological Fluids ◽

Bowel Diseases ◽

Therapeutic Molecules ◽

Inflammatory Bowel

To communicate with each other, cells release exosomes that transfer their composition, including lipids, proteins and nucleic acids, to neighboring cells, thus playing a role in various pathophysiological processes. During an infection with pathogenic bacteria, such as adherent-invasive E. coli (AIEC) associated with Crohn disease, exosomes secreted by infected cells can have an impact on the innate immune responses of surrounding cells to infection. Furthermore, inflammation can be amplified via the exosomal shuttle during infection with pathogenic bacteria, which could contribute to the development of the associated disease. Since these vesicles can be released in various biological fluids, changes in exosomal content may provide a means for the identification of non-invasive biomarkers for infectious and inflammatory bowel diseases. Moreover, evidence suggests that exosomes could be used as vaccines to prime the immune system to recognize and kill invading pathogens, and as therapeutic components relieving intestinal inflammation. Here, we summarize the current knowledge on the role of exosomes in bacterial infections and highlight their potential use as biomarkers, vaccines and conveyers of therapeutic molecules in inflammatory bowel diseases.

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Inflammatory Bowel Disease Etiology: Current Knowledge

Pteridines ◽

10.1515/pteridines-2018-0020 ◽

2018 ◽

Vol 29 (1) ◽

pp. 206-214 ◽

Cited By ~ 1

Author(s):

Justyna Kikut ◽

Nina Konecka ◽

Maciej Ziętek ◽

Małgorzata Szczuko

Keyword(s):

Inflammatory Bowel Diseases ◽

Depressive Disorders ◽

Current Knowledge ◽

The Body ◽

Disease Etiology ◽

Systemic Complications ◽

Nonalcoholic Fatty Liver ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Unclear Etiology

Abstract Non-specific inflammatory bowel diseases (IBD) include Crohn’s disease (CD) and ulcerative colitis (UC). Both diseases are characterized by chronic inflammation of unclear etiology. The inflammatory bowel diseases incidence is continuously observed to rise. Colon inflammatory response is a physiological process which occurrence is indispensable as an organisms’ defense reaction. The inflammation may be caused by internal factors associated with body’s cells as well as external factors, such as infections and exposition for inflammatory agents. Until recently, IBD have been classified as autoimmune diseases, today they seem to be associated with gut barrier disorders or dysbiosis. Factors that predispose to inflammatory bowel diseases include: genetic factors, dysbiosis and so called western-type diet, natural components such as gluten and lactose. In addition, the development of the disease is favored by: cigarette smoking, phosphate, nanomolecules, sodium chloride, emulgents, carrageenan, carboxymethylcellulose, pollution, maltodextrin. IBD affects whole the body, causing serious medical consequences. Symptoms like anxiety and chronic stress, that occur commonly, can lead to depressive disorders. Quantitative and qualitative dietary deficiency caused by absorption disorders, may promote the occurrence of osteoporosis and osteopenia. In addition, dysbiosis coexisting with alterations in intestinal permeability can lead to the development of nonalcoholic fatty liver disease. IBD medical consequences include also systemic complications, associated with the extra gastrointestinal manifestations’ occurrence.

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Diet, Gut Microbiome and Epigenetics: Emerging Links with Inflammatory Bowel Diseases and Prospects for Management and Prevention

10.20944/preprints201707.0039.v1 ◽

2017 ◽

Author(s):

Krasimira Aleksandrova ◽

Beatriz Romero ◽

Vicent Hernandez

Keyword(s):

Inflammatory Bowel Diseases ◽

Gut Microbiome ◽

Current Knowledge ◽

Health Concern ◽

Dietary Recommendations ◽

Nutritional Interventions ◽

Exclusive Enteral Nutrition ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Anti Inflammatory

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

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IL-36 cytokines in inflammatory and malignant diseases: not the new kid on the block anymore

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03909-4 ◽

2021 ◽

Author(s):

James Byrne ◽

Kevin Baker ◽

Aileen Houston ◽

Elizabeth Brint

Keyword(s):

Wound Healing ◽

Sequence Homology ◽

Inflammatory Bowel Diseases ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Malignant Diseases ◽

Bowel Diseases ◽

Health And Disease ◽

Inflammatory Bowel

AbstractThe IL-36 family of cytokines were first identified in 2000 based on their sequence homology to IL-1 cytokines. Over subsequent years, the ability of these cytokines to either agonise or antagonise an IL-1R homologue, now known as the IL-36 Receptor (IL-36R), was identified and these cytokines went through several cycles of renaming with the current nomenclature being proposed in 2010. Despite being identified over 20 years ago, it is only during the last decade that the function of these cytokines in health and disease has really begun to be appreciated, with both homeostatic functions in wound healing and response to infection, as well as pathological functions now ascribed. In the disease context, over activation of IL-36 has now been associated with many inflammatory diseases including Psoriasis and inflammatory bowel diseases, with roles in cancer also now being investigated. This review summarises the current knowledge of IL-36 biology, its role in inflammatory diseases and focuses on an emerging role for IL-36 in cancer.

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