The role of mast cells in functional GI disorders

Wouters, Mira M.; Vicario, María; Santos, Javier

doi:10.1136/gutjnl-2015-309151

Cited by 260 publications

(255 citation statements)

References 135 publications

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“…11,13 The density of MCs in both the small and large bowel may be increased in patients with IBS, but the results are somewhat inconsistent. Some studies demonstrated the number of MCs or the area of mucosa occupied by MCs was increased in IBS patients, 5 moreover, it varies in different genders, 15 in distinct bowel segments 16 and in subgroups of IBS with higher MCs counts in diarrhea-predominant IBS (D-IBS) patients than constipationpredominant IBS (C-IBS) patients.…”

Section: Mast Cells and Irritable Bowel Syndrome: The Presentmentioning

confidence: 96%

“…44 To a certain extent, IBS is related to food intolerance and/or allergy, 2,13,24 hence it may at least partly possess the common physiopathological mechanisms with allergic dysmotility. Although MCs only sporadically distribute in the inner and outer muscle layers, they may play a significant role in modulating the function of myenteric neurons and smooth muscles.…”

Section: Mast Cells Regulate Gastrointestinal Motilitymentioning

confidence: 99%

“…9,11,12 Other biological factors such as bacteria components (via Toll-like receptors or other pattern recognition receptors), and some physiochemical factors also could lead to MCs activation. 11,13 Upon activation, MCs release bioactive substances preformed in granules (histamine, enzymes, and heparin) and newly synthesized cytokine, chemokines, and lipid metabolites (Table 1). 4,9,10,14 These mediators contribute to the broad spectrum of regulating effects of MCs in the gut, and participate in multiple pathophysiological processes and diseases beyond allergy, which including IBS, functional dyspepsia, inflam- (CCL4), CCL5, CCL7, CCL8, CCL11, CCL13, CCL16, CCL17, CCL20, CCL22, CXCL1, CXCL2, CXCL3, CXCL10, MIF, LIF Growth factors VEGF, TGF-β, basic FGF, NGF, NT-3, GM-CSF, M-CSF, SCF, EGF, PDGF Eicosanoids Leukotrienes (LTB4, LTC4, LTD4, LTE4) Prostaglandins (PGD2, PGE2), PAF Other mediators Nitric oxide, SP, VIP, ATP, CRF, Urocortin TNF-α, tumor necrosis factor-α; IL, interleukins; VEGF, vascular endothelial growth factor; INF-γ, interferon-γ; CCL, chemokine (C-C motif) ligand; MCP, monocyte chemoattractant protein; MIP, macrophage inflammation protein; CXCL, chemokine (C-X-C motif) ligand; MIF, macrophage migration inhibitory factor; LIF, leukemia inhibitor factor; TGF-β, transforming growth factor-β; FGF, fibroblast growth factor; NGF, nerve growth factor; NT-3, neurotrophin-3; GM-CSF, granulocyte-macrophage colony stimulating factor; M-CSF, macrophage colony-stimulating factor; SCF, stem cell factor; EGF, epidermal growth factor; PDGF, platelet derived growth factor; LT, leukotrienes; PG, prostaglandins; PAF, platelet-activating factor; SP, substance P; VIP, vasoactive intestinal peptide; ATP, adenosine triphosphate; CRF, corticotropin releasing factor.…”

Section: Mast Cells In the Human Gutmentioning

confidence: 99%

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Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

107

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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Section: Mast Cells and Irritable Bowel Syndrome: The Presentmentioning

confidence: 96%

Section: Mast Cells Regulate Gastrointestinal Motilitymentioning

confidence: 99%

Section: Mast Cells In the Human Gutmentioning

confidence: 99%

See 1 more Smart Citation

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

107

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“…In support, IBS patients also show increased number and reactivity of mast cells. 28,29 Data from peripheral blood mononuclear cells, as well as in mucosal biopsies, from IBS patients show that cytokines levels including TNF-α, IL-1β and IL-6 are increased in IBS. [30][31][32][33] It is well recognized that proinflammatory cytokines can alter neurotransmitter release within the enteric nervous system to alter motility, secretion, and epithelial permeability via tight junction dysregulation to alter visceral sensitivity.…”

Section: Pathophysiology Of Irritable Bowel Syndrome: Activation Of Tmentioning

confidence: 99%

Mechanisms of Stress-induced Visceral Pain

Meerveld

Johnson

2018

J Neurogastroenterol Motil

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Evidence suggests that long-term stress facilitates visceral pain through sensitization of pain pathways and promotes chronic visceral pain disorders such as the irritable bowel syndrome (IBS). This review will describe the importance of stress in exacerbating IBS-induced abdominal pain. Additionally, we will briefly review our understanding of the activation of the hypothalamic-pituitary-adrenal axis by both chronic adult stress and following early life stress in the pathogenesis of IBS. The review will focus on the glucocorticoid receptor and corticotropin-releasing hormone-mediated mechanisms in the amygdala involved in stress-induced visceral hypersensitivity. One potential mechanism underlying persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in stress-induced visceral nociception, alterations in DNA methylation and histone acetylation patterns within the brain, have been linked to alterations in nociceptive signaling via increased expression of pro-nociceptive neurotransmitters. This review will discuss the latest studies investigating the long-term effects of stress on visceral sensitivity. Additionally, we will critically review the importance of experimental models of adult stress and early life stress in enhancing our understanding of the basic molecular mechanisms of nociceptive processing. Taken together, the complex clinical phenotype makes recapitulating IBS in rodent models extremely challenging. However, an aim of this review will be to describe how the use of rodent models of adult stress, early life stress (ELS), and a dysregulated HPA axis has improved our understanding of stress in the pathophysiology of IBS. Pathophysiology of Irritable Bowel Syndrome: Activation of the Brain-Gut AxisEvidence from clinical and basic research points to dysregulation of the bidirectional communication between the brain-gut axis in IBS. 21 The brain-gut axis represents a dynamic interplay between central circuits and peripheral mechanisms. The messengers of this complex circuit include neural, endocrine, metabolic, and immune mediators that are activated by central factors such as stress (Fig. 1). Although IBS is not an inflammatory disorder, the immune system plays a role in the pathogenesis of IBS in at least a subset of patients and likely contributes to the etiology of IBS symptoms. 22,23 A subset of IBS patients display a low grade chronic inflammation, and there is also evidence that following an enteric infection and combined with stressful life events, there is an increased risk of developed post-infectious IBS. [24][25][26][27] Clearly, the immune system and inflammatory processes are modulated by the HPA and autonomic nervous systems. In support, IBS patients also show increased number and reactivity of mast cells. 28,29 Data from peripheral blood mononuclear cells, as well as in mucosal biopsies, from IBS patients show that cytokines levels including TNF-α...

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“…64,67 In IBS, the mucosal inflammation is dominated by mast cells, eosinophils and intraepithelial lymphocytes, and it is now well established that such inflammation may cause visceral hypersensitivity, epithelial and neuromuscular dysfunction and subsequent altered peristalsis. 68 The immune system contains an immunologic archive, based on pattern recognition receptors that are able to destinguish potentially pathogenic microorganisms from harmless commensals. Among these receptors are the toll-like receptors (TLR) found on immune cells, enteroendocrine cells and neurons of the enteric nervous system (ENS).…”

Section: Ibs Microbiota and Inflammationmentioning

confidence: 99%

Irritable bowel syndrome, the microbiota and the gut-brain axis

Raskov¹,

et al. 2016

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Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brainaxis, and possible treatment modalities on irritable bowel syndrome. The integrated actions and communication between the microbiota and the autonomous nervous system are central players in the perpetuation of IBS symptoms. This signaling pathway is called the GutBrain Axis (GBA). The GBA is a bidirectional neurohumoral communication system that integrates brain and GI functions, such as gut motility, appetite and weightand here the microbiota plays a critical role. 2Changes in gastrointestinal or central nervous system physiology may result in an altered habitat, which again may cause changes in the composition of the microbiota.Disruption of the physiologic symbiotic relationship (eubiosis) between the human host and the microbiota is called dysbiosis and is regarded a basic factor for initiating and maintaining IBS in the majority of patients. Current evidence has suggested that the dysbiosis observed in IBS and the resulting immunological response may drive and perpetuate gastrointestinal symptoms of IBS suggesting that IBS is in fact a disorder of the microbiota and the GBA. It is unclear whether the initiating factor is brain abnormalities that drive the gut changes or if changes in the gut alter brain function through vagal and sympathetic pathways.3,4 The purpose of this article is to review recent research concerning the influence of microbiota and gut-brain-axis on IBS. IBSIt is estimated that approximately 10% of the World population and 15% of the population in the Western World suffer from IBS characterized by a mixture of recurrent abdominal pain, bloating, changing stool consistency such as diarrhea (IBS-D), constipation (IBS-C), or interchanging diarrhea and constipation (mixed-type or IBS-M), mucus secretion, and nausea. 5,6 Community-based data indicate that IBS-M is the most prevalent type followed by IBS-D and IBS-C and that switching among subtypes occurs. Bloating is the most prevalent symptom reported by 96% of patients with IBS of whatever subgroup. 7 In addition to abdominal symptoms, poor sleep, headache, CONTACT Hans Raskov raskov@mail.dk Lundevangsvej 23, DK-2900 Hellerup, Denmark. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/kgmi.

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The role of mast cells in functional GI disorders

Cited by 260 publications

References 135 publications

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Mechanisms of Stress-induced Visceral Pain

Irritable bowel syndrome, the microbiota and the gut-brain axis

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