title: Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome.
abstract: Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares. Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.
authors.affiliation: Maria M Buckley, Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Buckley
authors.affiliation: Maria M Buckley, Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland.
authors.forename: Siobhain M
authors.initials: SM
authors.lastname: O'Mahony
authors.affiliation: Maria M Buckley, Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland.
authors.forename: Dervla
authors.initials: D
authors.lastname: O'Malley
mesh_terms: D000818:Animals; D006801:Humans; D007107:Immune System / Q000378:metabolism / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000294:innervation*; D043183:Irritable Bowel Syndrome / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000276:immunology / Q000503:physiopathology; D009490:Neurosecretory Systems / Q000378:metabolism / Q000503:physiopathology*; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction
keywords: Corticotropin-releasing factor; Enteric nervous system; Pro-inflammatory cytokines; Stress; Vagus
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