Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots: Stress, intestinal hyperpermeability and inflammation

Farhadi, Ashkan; Fields, Jeremy Z.; Keshavarzian, Ali

doi:10.3748/wjg.v13.i22.3027

Cited by 75 publications

(33 citation statements)

References 45 publications

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“…First, the mucosal levels of mast cell tryptase and histamine, two proteases that are released upon activation, were consistently observed to be increased in IBS patients presenting higher mast cell numbers. 63,71,73,74,81,83,84 Moreover, such mast cell products can induce the permeabilisation of the intestinal epithelium, 115 and increased gut permeability in IBS patients is a robust finding (see Table 3). Two studies have reported a correlation between mast cell density and increased intestinal permeability in IBS patients.…”

Section: Immune Activation In Ibs Patientsmentioning

confidence: 99%

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Matricon

Méleine

Gelot

et al. 2012

Aliment Pharmacol Ther

185

180

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This uncommissioned review article was subject to full peer-review. SUMMARY BackgroundIrritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. AimTo determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. MethodsThe scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. ResultsImmune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. ConclusionsThe changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology.

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Section: Immune Activation In Ibs Patientsmentioning

confidence: 99%

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Matricon

Méleine

Gelot

et al. 2012

Aliment Pharmacol Ther

185

180

View full text Add to dashboard Cite

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“…Enhanced intestinal permeability in this population is considered an initial event because it is increased in first-degree relatives of Crohn's disease patients. 140,141 Several observations link clinical relapses to the increase in intestinal permeability 142,143 and to life stress, 144,145 partly through mast cell activation 146 and the release of CRF from eosinophils 83 and neighboring nerves. 68 Moreover, inflammatory Public speech and CRF administration increased intestinal permeability and salivary cortisol.…”

Section: Clinical Consequences Of Stress/ Corticotropin-releasing Facmentioning

confidence: 99%

Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

Rodiño-Janeiro¹,

Alonso-Cotoner²,

Pigrau³

et al. 2015

J Neurogastroenterol Motil

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The interface between the intestinal lumen and the mucosa is the location where the majority of ingested immunogenic particles face the scrutiny of the vast gastrointestinal immune system. Upon regular physiological conditions, the intestinal microflora and the epithelial barrier are well prepared to process daily a huge amount of food-derived antigens and non-immunogenic particles. Similarly, they are ready to prevent environmental toxins and microbial antigens to penetrate further and interact with the mucosal-associated immune system. These functions promote the development of proper immune responses and oral tolerance and prevent disease and inflammation. Brain-gut axis structures participate in the processing and execution of response signals to external and internal stimuli. The brain-gut axis integrates local and distant regulatory networks and supersystems that serve key housekeeping physiological functions including the balanced functioning of the intestinal barrier. Disturbance of the brain-gut axis may induce intestinal barrier dysfunction, increasing the risk of uncontrolled immunological reactions, which may indeed trigger transient mucosal inflammation and gut disease. There is a large body of evidence indicating that stress, through the brain-gut axis, may cause intestinal barrier dysfunction, mainly via the systemic and peripheral release of corticotropin-releasing factor. In this review, we describe the role of stress and corticotropin-releasing factor in the regulation of gastrointestinal permeability, and discuss the link to both health and pathological conditions. (J Neurogastroenterol Motil 2015;21:33-50)

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“…Chronic stress is a major risk factor for FGIDs, likely through dysregulation of the brain-gut axis via the hypothalamic-pituitary axis [51]. This in turn may lead to increased intestinal permeability, resulting in enhanced uptake of potentially noxious agents [52], disordered motility [53] and visceral hypersensitivity [54] with mast cell degranulation and activation of an inflammatory state [55].…”

Section: Stress and The Brain-gut Axismentioning

confidence: 99%

Therapeutic strategies for functional dyspepsia and irritable bowel syndrome based on pathophysiology

2015

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Functional gastrointestinal disorders (FGIDs) are common and distressing. They are so named because a defined pathophysiology in terms of structural or biochemical pathways is lacking. Traditionally FGIDs have been conceptualized as brain-gut disorders, with subgroups of patients demonstrating visceral hypersensitivity and motility abnormalities as well as psychological distress. However, it is becoming apparent that there are certain structural or biochemical gut alterations among subsets with the common FGIDs, most notably functional dyspepsia (FD) and irritable bowel syndrome (IBS). For example, a sodium channel mutation has been identified in IBS that may account for 2 % of cases, and subtle intestinal inflammation has been observed in both IBS and FD. Other research has implicated early life events and stress, autoimmune disorders and atopy and infections, the gut microbiome and disordered mucosal immune activation in patients with IBS or FD. Understanding the origin of symptoms in FGIDs will allow therapy to be targeted at the pathophysiological changes, not at merely alleviating symptoms, and holds hope for eventual cure in some cases.For example, there are promising developments in manipulating the microbiome through diet, prebiotics and antibiotics in IBS, and testing and treating patients for Helicobacter pylori infection remains a mainstay of therapy in patients with dyspepsia and this infection. Locally acting drugs such as linaclotide have been an advance in treating the symptoms of constipation-predominant IBS, but do not alter the natural history of the disease. A role for a holistic approach to patients with FGIDs is warranted, as brain-togut and gut-to-brain pathways appear to be activated.

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Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots: Stress, intestinal hyperpermeability and inflammation

Cited by 75 publications

References 45 publications

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

Therapeutic strategies for functional dyspepsia and irritable bowel syndrome based on pathophysiology

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