Author(s): Peter Layer [*] 1
antidepressant; antispasmodic; constipation; guanylate cyclase C agonist; irritable bowel syndrome; laxative; linaclotide; probiotic; prokinetics; secretagog
Irritable bowel syndrome: a complex disorder with interacting mechanisms
Irritable bowel syndrome (IBS) is thought to result from the complex interplay of abnormal gut motility and visceral hypersensitivity, which manifests in abdominal pain and discomfort symptoms [1,2] , as well as interacting psychosocial factors such as stressful life events that may trigger or exacerbate symptoms [2-4] . Of note, these factors are not specific to IBS but may also be contributing factors to other chronic bowel diseases  .
Exactly how these factors interplay in the pathophysiology of IBS is not completely understood and is the subject of ongoing research. Best characterized is the pathogenic model of postinfectious IBS, which may give clues to the underlying mechanism of general IBS and is therefore described here in more detail as an example for general IBS. Postinfectious IBS can occur after acute severe gastroenteritis and can persist for years after the original infection has subsided [6-8] . The main risk factors for postinfectious IBS are bacterial toxins (relative risk [RR]: 12.8) and the duration of the infection (RR: 11.4 for illness lasting >3 weeks vs illness lasting 60 years of age) was associated with a lower risk (RR: 0.36)  . The probable trigger of postinfectious IBS is thought to be enteric damage causing disturbances of the intestinal barrier. This may lead to prolonged immune activation, which in turn may sustain a low-grade inflammation of the colon. In support of this hypothesis, colonic biopsies from patients with IBS expressed higher amounts of the proinflammatory cytokines  but reduced amounts of chemokines crucial for the mucosal immune response  . Moreover, some studies found that the number of activated mast cells in the colon of patients with IBS was increased and that their proximity to colonic nerves correlated with abdominal pain [13,14] .
Management strategy for irritable bowel syndrome
A positive patient-physician relationship is key to the successful management of IBS (Figure 1)  . It is important that physicians effectively communicate a plausible disease model and treatment concept to ensure patients are aware of the shortcomings of current diagnostic and therapeutic tools [5,16,17] . In particular, patients should be reassured that, while their symptoms are distressing and appear worrying, IBS is a benign disorder and not a precursor of a life-threatening disease. The physician and patient together should try to identify specific aggravating trigger factors, such as dietary, lifestyle and psychological factors. Treatment options focus on symptomatic relief of the main symptoms. Moreover, as a rule, the management of IBS currently follows a trial-and-error approach during which treatments are evaluated systematically, based on symptom relief and tolerability. In the absence of response to available therapies, patients should be encouraged to consider participation in controlled clinical trials to evaluate new treatment options.
Psychological factors, lifestyle & diet
Psychosocial factors have been implicated in the development of IBS and may affect the severity of IBS symptoms  . Therefore, psychological therapies may play an important...