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      Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use

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          Abstract

          Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells’ activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms.

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          Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis.

          Many cross-sectional surveys have reported the prevalence of irritable bowel syndrome (IBS), but there have been no recent systematic review of data from all studies to determine its global prevalence and risk factors. MEDLINE, EMBASE, and EMBASE Classic were searched (until October 2011) to identify population-based studies that reported the prevalence of IBS in adults (≥15 years old); IBS was defined by using specific symptom-based criteria or questionnaires. The prevalence of IBS was extracted for all studies and based on the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Of the 390 citations evaluated, 81 reported the prevalence of IBS in 80 separate study populations containing 260,960 subjects. Pooled prevalence in all studies was 11.2% (95% CI, 9.8%-12.8%). The prevalence varied according to country (from 1.1% to 45.0%) and criteria used to define IBS. The greatest prevalence values were calculated when ≥3 Manning criteria were used (14%; 95% CI, 10.0%-17.0%); by using the Rome I and Rome II criteria, prevalence values were 8.8% (95% CI, 6.8%-11.2%) and 9.4% (95% CI, 7.8%-11.1%), respectively. The prevalence was higher for women than men (OR, 1.67; 95% CI, 1.53-1.82) and lower for individuals older than 50 years, compared with those younger than 50 (OR, 0.75; 95% CI, 0.62-0.92). There was no effect of socioeconomic status, but only 4 studies reported these data. The prevalence of IBS varies among countries, as well as criteria used to define its presence. Women are at slightly higher risk for IBS than men. The effects of socioeconomic status have not been well described. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
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            Regulation of Inflammation by Short Chain Fatty Acids

            The short chain fatty acids (SCFAs) acetate (C2), propionate (C3) and butyrate (C4) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted.
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              Identification of a mast cell specific receptor crucial for pseudo-allergic drug reactions

              Mast cells are primary effectors in allergic reactions, and may have significant roles in diseases by secreting histamine and various inflammatory and immunomodulatory substances 1,2 . While classically they are activated by IgE antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions 1,3 . Roles for these substances in pathology have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, MrgprB2, the orthologue of the human G-protein coupled receptor (GPCR) MrgprX2. Secretagogue-induced histamine release, inflammation, and airway contraction are abolished in MrgprB2 null mutant mice. Further, we show that most classes of FDA-approved peptidergic drugs associated with allergic-type injection-site reactions also activate MrgprB2 and MrgprX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that MrgprB2 and MrgprX2 are targets of many small molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice, and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MrgprX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                20 September 2020
                September 2020
                : 25
                : 18
                : 4314
                Affiliations
                [1 ]High Performance Research Group in Physiopathology and Pharmacology of the Digestive System NeuGut-URJC, Department of Basic Health Sciences, Faculty of Health Sciences, Universidad Rey Juan Carlos (URJC), Campus de Alcorcón, Avda. de Atenas s/n, 28022 Madrid, Spain; jose.uranga@ 123456urjc.es
                [2 ]Department of Cell Biology, Physiology and Immunology, Neurosciences Institute, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; vicente.martinez@ 123456uab.es
                [3 ]Center for Networked Biomedical Research on Liver and Digestive Diseases (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
                [4 ]Associated Unit to Institute of Medicinal Chemistry (Unidad Asociada I+D+i del Instituto de Química Médica, IQM), Spanish National Research Council (Consejo Superior de Investigaciones Científicas, CSIC), 28006 Madrid, Spain
                Author notes
                [* ]Correspondence: raquel.abalo@ 123456urjc.es ; Tel.: +34-914-888854
                Author information
                https://orcid.org/0000-0003-4656-8569
                https://orcid.org/0000-0001-5193-715X
                https://orcid.org/0000-0002-6726-8795
                Article
                molecules-25-04314
                10.3390/molecules25184314
                7570512
                32962285
                1503fdd9-e88d-4c7c-91c2-0eb26394fc95
                © 2020 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
                : 30 July 2020
                : 17 September 2020
                Categories
                Review

                cannabidiol,fatty acids,heparin,histamine,irritable bowel syndrome,mast cells,nerve growth factor,nutraceuticals,polyphenols,visceral pain

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