Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome (original) (raw)
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BIOLOGICAL INTERACTION OF STRESS AND IRRITABLE BOWEL SYNDROME
A variety of stressors play a role in the development of irritable bowel syndrome. Irritable bowel syndrome is a biopsychosocial disorder that results from dysregulation of central or enteric nervous system function. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional, and pain modulatory responses. Certain investigational studies reported to date indicate that the activation of CRF1 pathways may result in a combination of effects that are key features of symptoms in some irritable bowel syndrome patients. These include stimulation of colonic motility, defecation or watery diarrhea, gut hypersensitivity that increases the perception of stimuli within the bowel, focused attention (hypervigilance) toward the gut sensations, and mast cell activation. Blocking the CRF1 receptors may alleviate all these effects. Stress thus can be included in an integrative model explaining the pathophysiology of functional bowel disorder. Advances in the understanding of the relationship between stress and visceral perception may constitute a basis for a therapeutic approach of functional bowel disorders targeted on the central nervous system.
The neurobiology of irritable bowel syndrome
Molecular Psychiatry
Irritable bowel syndrome (IBS) is the most prevalent disorder of brain-gut interactions that affects between 5 and 10% of the general population worldwide. The current symptom criteria restrict the diagnosis to recurrent abdominal pain associated with altered bowel habits, but the majority of patients also report non-painful abdominal discomfort, associated psychiatric conditions (anxiety and depression), as well as other visceral and somatic pain-related symptoms. For decades, IBS was considered an intestinal motility disorder, and more recently a gut disorder. However, based on an extensive body of reported information about central, peripheral mechanisms and genetic factors involved in the pathophysiology of IBS symptoms, a comprehensive disease model of brain-gut-microbiome interactions has emerged, which can explain altered bowel habits, chronic abdominal pain, and psychiatric comorbidities. In this review, we will first describe novel insights into several key components of br...
Neuroendocrine Dysregulation in Irritable Bowel Syndrome Patients: A Pilot Study
Journal of neurogastroenterology and motility, 2017
Irritable bowel syndrome (IBS) is a multifactorial disorder, involving dysregulation of brain-gut axis. Our aim was to evaluate the neuroendocrine activity in IBS. Thirty IBS and 30 healthy subjects were enrolled. Psychological symptoms were evaluated by questionnaires. Urinary 5-hydroxyindoleacetic acid (5-HIAA), plasma serotonin, endothelin, neuropeptide Y (NPY), plasma, and urinary cortisol levels were evaluated. Fourteen IBS subjects underwent microneurography to obtain multiunit recordings of efferent postganglionic muscle sympathetic nerve activity (MSNA). Prevalent psychological symptoms in IBS were maladjustment (60%), trait (40%) and state (17%) anxiety, obsessive compulsive-disorders (23%), and depressive symptoms (23%). IBS showed increased NPY (31.9 [43.7] vs 14.8 [18.1] pmol/L, P = 0.006), serotonin (214.9 [182.6] vs 141.0 [45.5] pg/mL, P = 0.010), and endothelin [1.1 [1.4] vs 2.1 [8.1], P = 0.054], compared to healthy subjects. Moreover, plasma NPY, endothelin, cortiso...
Neuroendocrine markers and psychological features in patients with irritable bowel syndrome
International Journal of Colorectal Disease, 2013
Background and aims The key role of the brain-gut axis in the pathophysiology of irritable bowel syndrome (IBS) has been recognized. The aim of this study was to assess the possible association between IBS, neuroendocrine markers, and psychological features. Methods One hundred and twenty-five consecutive IBS patients and 105 healthy subjects were enrolled. Plasma serotonin, plasma and urinary cortisol, and plasma neuropeptide Y levels were evaluated. All patients were given a questionnaire to assess IBS symptom severity. In 66 patients, a psychodiagnostic assessment was carried out. Results A high incidence of specific psychological features, including state anxiety (69.69 %), trait anxiety (54.54 %), obsessions and compulsions (28.78 %), was observed in IBS patients. A positive correlation between neuropeptide Y and state anxiety (r=0.287, p=0.024) and simulation/social ingenuity (r = 0.269, p = 0.039) was found in these patients. In diarrhea-predominant IBS, plasma cortisol was linearly related to plasma serotonin (r=0.5663, p<0.001). Conclusions In IBS patients, a significant correlation was found between specific psychological features and neuroendocrine markers, especially plasma cortisol and neuropeptide Y; in diarrhea-predominant IBS, a correlation between plasma cortisol and serotonin was found, although it needs to be confirmed in more extensive cohorts.
International Journal of Psychophysiology, 2012
Objective: In this study, we investigated levels and relative ratios of adrenal hormones (including cortisol, dehydroepiandrosterone [DHEA], and DHEA-sulfate [DHEA-S]) and their psychophysiological correlates under acute psychosocial stress in individuals with irritable bowel syndrome (IBS). Methods: Fifty-three college students participated in the study (male: 42, female: 11; mean age: 22.64 years), including 13 individuals with IBS (IBS group) and 40 individuals without IBS (control group). The participants were exposed to a standardized laboratory stressor, which included delivering a speech and performing a mental arithmetic task. We measured subjective stress levels and salivary cortisol, DHEA, and DHEA-S levels at relevant time points before, during, and after the tasks. Results: DHEA-S level and the DHEA-S/DHEA ratio in the IBS group were significantly lower than those in the control group, and the cortisol/DHEA-S ratio in the IBS group was higher than that in the control group throughout the experiment. In the IBS group, the appraisal of a threat was positively correlated with cortisol levels (r = 0.61), and the appraisal of controllability was negatively correlated with cortisol levels (r = − 0.64) and with the cortisol/DHEA ratio (r = − 0.71). The control group showed a significant positive correlation between the appraisal of threat and cortisol levels (r = 0.32). Conclusion: The present study indicates that individuals with IBS had lower DHEA-S levels, and that their stressful cognitive appraisals under acute psychosocial stress caused the effects of cortisol to dominate. This adrenal hormone response may be involved in exacerbating abdominal symptoms in individuals with IBS.
Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?
The American Journal of Gastroenterology, 2013
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.
World journal of gastroenterology : WJG, 2011
Irritable bowel syndrome (IBS) is defined by the Rome III criteria as symptoms of recurrent abdominal pain or discomfort with the onset of a marked change in bowel habits with no evidence of an inflammatory, anatomic, metabolic, or neoplastic process. As such, many clinicians regard IBS as a central nervous system problem of altered pain perception. Here, we review the recent literature and discuss the evidence that supports an organic based model, which views IBS as a complex, heterogeneous, inter-dependent, and multi-variable inflammatory process along the neuronal-gut axis. We delineate the organic pathophysiology of IBS, demonstrate the role of inflammation in IBS, review the possible differences between adult and pediatric IBS, discuss the merits of a comprehensive treatment model as taught by the Institute of Functional Medicine, and describe the potential for future research for this syndrome.