Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions

Öhman, Lena; Simrén, Magnus

doi:10.1038/nrgastro.2010.4

Cited by 532 publications

(478 citation statements)

References 113 publications

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“…Th e gastrointestinal (GI) tract contains extensive immune and nervous systems (outlined in Figure 1 ), and alterations in the immune system are increasingly implicated in the pathogenesis of IBS ( 2 ). Th is was fi rst observed in patients that attributed their symptoms to prior exposure to a GI pathogen, termed post-infectious IBS, but more recently has also been shown in other IBS cohorts ( 2,3 ). Surprisingly, little is known of how changes in the immune function aff ect the nerve function in IBS.…”

Section: Introductionmentioning

confidence: 99%

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

133

117

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Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterized by pain or discomfort from the lower abdominal region, which is associated with altered bowel habit. Despite its prevalence, there is currently a lack of effective treatment options for patients. IBS has long been considered as a neurological condition resulting from alterations in the brain gut axis, but immunological alterations are increasingly reported in IBS patients, consistent with the hypothesis that there is a chronic, but low-grade, immune activation. Mediators released by immune cells act to either dampen or amplify the activity of GI nerves. Release of a number of these mediators correlates with symptoms of IBS, highlighting the importance of interactions between the immune and the nervous systems. Investigation of the role of microbiota in these interactions is in its early stages, but may provide many answers regarding the mechanisms underlying activation of the immune system in IBS. Identifying what the key changes in the GI immune system are in IBS and how these changes modulate viscerosensory nervous function is essential for the development of novel therapies for the underlying disorder.

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Section: Introductionmentioning

confidence: 99%

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

133

117

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“…However, it is widely viewed as a disorder caused by a dysregulation of the complex interactions that exist along the brain-gut axis (Grenham et al 2011). Altered hypothalamic-pituitary-adrenal (HPA) axis function (Mayer, 2000), autonomic dysfunction (Tillisch et al 2005), immune activation (Ohman & Simren, 2010) and heightened central pain sensitivity (Mayer et al 2009) are considered key pathophysiological features related to abnormal brain-gut interactions in IBS. Observational studies have identified that stressors, such as early life trauma (Chitkara et al 2008) or chronic stressful life events experienced in adolescence or adulthood (Blanchard et al 2008), are major risk factors for IBS.…”

Section: Introductionmentioning

confidence: 99%

A sustained hypothalamic–pituitary–adrenal axis response to acute psychosocial stress in irritable bowel syndrome

et al. 2014

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Background. Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS.Method. Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre-and post-exposure to the TSST.Results. The hypothalamic-pituitary-adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUC G ) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups.Conclusions. Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.

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“…In recent years, IBS is increasingly viewed as a low grade inflammatory disorder, 3 and attentions have been focused on the roles of mast cells (MCs) in the gut wall, accounting for the close relations of MCs with major intestinal functions, such as epithelial secretion, epithelial permeability, blood flow, neuroimmune interactions, visceral sensation, and peristalsis. 4 MCs hyperplasia and activation lead to abnormal gastrointestinal sensitivity, motility, and secretion, which in turn contribute to the hallmark symptoms of IBS-abdominal pain and/or discomfort, bloating, and abnormal bowel function (diarrhea and/or constipation).…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

111

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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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Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions

Cited by 532 publications

References 113 publications

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

A sustained hypothalamic–pituitary–adrenal axis response to acute psychosocial stress in irritable bowel syndrome

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

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