Zsa Zsa Weerts

Chapter 1 12 It is well-recognized that IBS is associated with a pronounced interference with daily life activities and a decrease in quality of life (QoL) 25,32,33 , with QoL scores comparable to or even lower than in patients with GERD, diabetes, migraine, and asthma. 34 When applying the ‘time-trade-off method’, the mean reported QoL scores of an IBS patient correspond to a 35-year-old patient willing to sacrifice 10-15 years of the remaining 40 years (of life expectancy) in exchange for immediate perfect health. 25,35 Albeit hypothetical, this clearly demonstrates the considerable burden experienced by these patients. Pathophysiology of IBS Although the pathophysiology of IBS is complex, multifactorial, and incompletely understood, there is now substantial evidence for several mechanisms to be involved. Risk factors for IBS include female sex, a history of GI infections, previous abdominal surgery, use of antibiotics, somatic pain ( e.g. migraine), endometriosis, and psychological factors, such as acute psychological stress, a history of stressful life events or sexual abuse, the presence of anxiety, depression, and somatization. 18 Furthermore, research data strongly suggests that a aberrant brain-gut-interaction has a central pathophysiologic role. Other factors implicated in IBS pathophysiology include visceral hypersensitivity, genetic susceptibility, disturbed intestinal motility, low grade immune activation, intestinal dysbiosis, excess fermentation by colonic microbiota, impaired gas tolerance, abdomino-phrenic dyssynergia, alterations in bile-acid metabolism, and psychological comorbidities. 5,6,18 It is assumed that several mechanisms, when present at the same time, lead to symptoms in the individual patient with IBS. These symptoms and underlying factors differ between subgroups of IBS. 10 The pathophysiology of IBS is depicted schematically in Figure 1.1 . Some of the key-mechanisms involved will be described in the following paragraphs. Altered brain-gut-interaction is a key factor that likely contributes to abdominal pain, which is a typical hallmark of IBS. Thresholds for abdominal pain are lowered (allodynia) and abdominal pain levels are higher (hyperalgesia) in patients with visceral hypersensitivity, which can be measured using the barostat procedure. The proportion of IBS patients with visceral hypersensitivity varies between studies and ranges to up to 60%. 36 Viscero-sensory function entails a bidirectional interaction between the enteric and spinal nerves and the central nervous system. From the gut, visceral stimuli travel from nerve endings located in all layers of the intestinal wall and mesentery 37 to afferent neurons residing in the dorsal root ganglia. 38 From the dorsal horn, afferent input is conveyed via spinal pathways to subcortical regions such as the nucleus of the solitary