Mucosal Immune Cell Numbers and Visceral Sensitivity in Patients With Irritable Bowel Syndrome: Is There Any Relationship?

Braak, Breg; Klooker, Tamira K.; Wouters, Mira M.; Welting, Olaf; Loos, Chris M. van der; Stanisor, Oana I.; Diest, Sophie van; Wijngaard, René M. van den; Boeckxstaens, Guy E.

doi:10.1038/ajg.2012.54

Cited by 86 publications

(112 citation statements)

References 66 publications

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“…Braak et al ( 8 ) also conclude that a decrease in mast cells found might indicate a dysregulation of the immune system. However, it is important to note that mast cell numbers in volunteers were high with a wide range of values.…”

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confidence: 95%

“…CRH signaling pathways have been shown to have an important role in stress-related alterations of gut function related to intestinal symptoms ( 7 ). Braak et al ( 8 ) have attempted to clarify IBS pathophysiology using these strategies.…”

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confidence: 99%

“…Increased numbers of mast cells have been reported in the terminal ileum in patients with IBS, although there was lack of correlation with diarrhea-predominant IBS symptoms ( 4 ). Braak et al ( 8 ) conclude that the number of mast cells, macrophages (CD68), T cells (CD3 and CD8), and λ FLC-positive mast cells is decreased in IBS patients compared with healthy volunteers. As a general statement, this needs clarifi cation.…”

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confidence: 99%

“…Braak et al ( 8 ) ask us to question the role of microscopic infl ammation (they defi ne this as an increased number of infl ammatory cells) as a pathophysiological mechanism of visceral hypersensitivity in IBS. It is unlikely that most colleagues will now dismiss a role of infl ammation in IBS.…”

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confidence: 99%

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Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

Theoharides¹,

Asadi²,

Chen³

et al. 2012

American Journal of Gastroenterology

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Irritable bowel syndrome (IBS) is the most common condition seen by gastroenterologists. It presents with alternating symptoms of bowel dysfunction that often worsens with stress. The cause of these symptoms eludes investigators and many attempts have been made to discover an underlying pathology. This is a daunting task since symptoms come and go, and change characteristics. Furthermore, the pathology of IBS is unlikely to be identical in all patients. In addition, all symptoms and all features studied thus far have a strong overlap with healthy volunteers. Elsewhere in this issue, Braak et al. report a well-designed clinical investigation in patients with IBS and come to the conclusion that IBS is not characterized by mast cell or other immune cell proliferation, but by immune dysregulation in the colon. Is this the fi nal answer? Am J Gastroenterol 2012; 107:727 -729; doi: 10.1038/ajg.2012 Irritable bowel syndrome (IBS) is a common functional disorder in the West ( 1 ) and in Asia ( 2 ), which is characterized clinically as abdominal discomfort or pain with alternating constipation and diarrhea. Mechanistic pathways to symptom generation are unclear, although dysfunction of brain-gut communication, gut motility, visceral perception, neuroimmune responses, infl ammation, and mucosal integrity, as well as the psychosocial status might be involved ( 3 ). Th e mucosa contains endings of the enteric sensory nerves; these aff erent nerves can modify motility and pain perception. Th erefore, immune cell infi ltration assessed in mucosal biopsies may provide critical information on the mechanisms of symptom generation. Both intestinal ( 4 ) and colonic ( 5,6 ) biopsies have been investigated. Mast cells have received particular attention because its secretory products, such as histamine, prostaglandins, and proteinases, are capable of sensorimotor dysfunction. IBS appears to worsen with stress and the important information might be obtained from relationships between stress, corticotropin-releasing hormone (CRH) and symptoms ( 7 ). CRH signaling pathways have been shown to have an important role in stress-related alterations of gut function related to intestinal symptoms ( 7 ). Braak et al. ( 8 ) have attempted to clarify IBS pathophysiology using these strategies.Mast cells are well known to modulate gastrointestinal pathophysiology and are considered to be involved in IBS ( 9 ). Increased numbers of mast cells have been reported in the terminal ileum in patients with IBS, although there was lack of correlation with diarrhea-predominant IBS symptoms ( 4 ). Braak et al. ( 8 ) conclude that the number of mast cells, macrophages (CD68), T cells (CD3 and CD8), and λ FLC-positive mast cells is decreased in IBS patients compared with healthy volunteers. As a general statement, this needs clarifi cation. Th ey note the decrease in the descending colon, but no change was seen in the ascending colon and immune cell numbers in the small intestine were not measured. Furthermore, mast cells in the gut musculature ( ...

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confidence: 95%

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confidence: 99%

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Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

Theoharides¹,

Asadi²,

Chen³

et al. 2012

American Journal of Gastroenterology

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“…Th ey also suggest that cysteine as well as serine proteases may be involved in this process -an interesting fi nding given the presence of cysteine proteases in intestinal cells other than mast cells, the dominant source of serine proteases. Th e role of mast cells in IBS has been the subject of considerable interest and, although some have reported increased mast cell numbers and / or activation in IBS ( 22 -25 ), this fi nding has not been universal ( 26,27 ). Th e observation that proteases other than those derived from mast cells could be involved in neuronal eff ects mediated by IBS supernatants is an important one but the possibility that these proteases could be of bacterial origin also needs to be considered ( 28 ).…”

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Editorial: PARs for the Course: Roles of Proteases and PAR Receptors in Subtly Inflamed Irritable Bowel Syndrome

Quigley

2013

American Journal of Gastroenterology

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Although the etiology of irritable bowel syndrome (IBS) remains unknown, clinical and laboratory observations suggest that within the broad and varying phenotype, that is, IBS, there may exist subgroups, which can be defi ned on the basis of a distinctive pathophysiological basis. Of these, postinfectious IBS is the best characterized; in IBS, in general, studies of infl ammatory mediators and substances elaborated by cells involved in the intestinal immune response, such as proteases, suggest that some IBS sufferers can be differentiated on the basis of an aberrant immune response. Valdez-Morales and colleagues extend this concept by demonstrating the ability of supernatants of biopsy cultures from individuals with diarrheapredominant IBS to enhance neuronal excitabilityan effect that could well contribute to a clinical hallmark of IBS, namely, visceral hypersensitivity. Am J Gastroenterol 2013; 108:1644 -1646 doi: 10.1038/ajg.2013 Irritable bowel syndrome (IBS) is a common and, at times, disabling condition whose etiology, despite the best eff orts of clinicians and scientists, remains unclear. As a consequence, reliable biomarkers for the syndrome have yet to emerge, and its diagnosis, therefore, continues to rest on clinical features and the exclusion of disorders that have the potential to present in a similar manner ( 1 ). Much of the diffi culties related to unraveling the enigma that is IBS revolve around its heterogeneity, which may originate from any one or a combination of the following: dominant symptom (pain, discomfort, bloating, distension, and altered bowel habit), predominant bowel habit (diarrhea, constipation, or mixed pattern), comorbidity (be it psychological or somatic), severity (including impact on the quality of life), natural history, and prognosis. To frustrate the clinician scientist further, those IBS subtypes that can be defi ned with some degree of accuracy, at least using Rome III criteria (2), including diarrhea-predominant IBS, constipationpredominant IBS and mixed IBS, do not appear to be immutable, and suff erers can move from one stool pattern to another over time, thus emphasizing the importance of longitudinal studies of this disorder ( 3,4 ).However, in this rather gloomy scenario, shines an unexpected beam of light that has illuminated (or, to be accurate, reignited) a new perspective on the etiology of IBS -postinfectious IBS (PI-IBS) ( 5 ). Although PI-IBS had been well described decades beforehand ( 6 ), more recent studies based on the consequences of large-scale outbreaks of bacterial, viral, and amebic gastroenteritis have firmly brought the concept of host -microbiome interactions into play in IBS research, in general ( 7 ). Observations in relation to PI-IBS, such as the description of correlations between the initial inflammatory response to the infection and the subsequent development of IBS ( 8 ), as well as the identification of polymorphisms in genes coding for components of the mucosal immune response and intestinal barrier integrity as risk factor...

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Irritable Bowel Syndrome

Videlock¹,

Chang²

2015

Yamada' S Textbook of Gastroenterology

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Mucosal Immune Cell Numbers and Visceral Sensitivity in Patients With Irritable Bowel Syndrome: Is There Any Relationship?

Cited by 86 publications

References 66 publications

Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

Editorial: PARs for the Course: Roles of Proteases and PAR Receptors in Subtly Inflamed Irritable Bowel Syndrome

Irritable Bowel Syndrome

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