List of abbreviations
EGG, electrogastrography; GI, gastrointestinal; HAPC, high-amplitude propagating contraction; IBS, irritable bowel syndrome; MMC, migrating motor complex; SIBO, small intestinal bacterial overgrowth.
Irritable bowel syndrome (IBS) is characterized by pain and discomfort in the abdomen related to abnormal bowel habits [1]. It is one of the most common disorders encountered by gastroenterologists [2], [3] and also one of most common gastrointestinal disorders managed by general practitioners [4]. Unfortunately, truly effective therapeutic options for these patients are rare, and recent attempts to launch new treatment options have been disappointing [5], [6]. The prevalence of IBS varies depending on the diagnostic criteria used, but it appears to affect up to 20% of the population at any given time [7], [8], [9], [10]. Due to its high prevalence and, for many patients, chronic nature and incapacitating symptoms the cost of IBS to society is substantial, and IBS profoundly affects the daily lives of many patients leading to a low quality of life [11]. Therefore, both from an economical and humanitarian point of view, more effective treatment alternatives are needed for IBS.
Despite being very common, the pathophysiology of IBS is incompletely understood, which poses problems in the search for effective therapeutic alternatives. Altered psychosocial function, disturbed gastrointestinal (GI) motility and visceral hypersensitivity are considered to be important mechanisms involved in the pathophysiology of IBS [12]. However, none of these explain all the different symptoms in IBS and the relative importance of central versus peripheral factors for the various symptoms in IBS is much debated and not entirely known. In an attempt to understand the interaction between central and peripheral pathophysiological factors, a more integrated model of brain–gut interactions proposes that the central and enteric nervous systems interact and modulate altered motility, abnormal sensation and autonomic reactivity: the brain–gut axis [13]. Recent studies have provided evidence that IBS is due to a dysregulation of the brain–gut axis, with peripheral alterations probably dominating in some patients and disturbed central processing of signals from the periphery dominating in others. Still, factors in the periphery, such as visceral hypersensitivity, and abnormal GI motility and secretion are considered to be key factors in the pathophysiology, contributing to the main symptoms of IBS, i.e. abdominal pain/discomfort, bloating and abnormal bowel function resulting in diarrhoea and/or constipation. However, it should be stressed that this does not negate the importance of central mechanisms in IBS as well.
This article will review the literature on findings in IBS patients supporting involvement of peripheral factors in the pathophysiology of IBS. During recent years low-grade inflammation and alterations in the gut flora are other peripheral factors found to be of potential importance for IBS, but they will be reviewed elsewhere in this publication, and are therefore not discussed in detail in this review.
The hallmark symptoms of IBS are likely to have their origin in the large and small bowel, but upper GI symptoms are also frequently reported by IBS patients [14]. Therefore, even though most studies of motility in IBS have focused on the large and small bowel, there are also reports on disturbed motility in the oesophagus and the stomach. Patients with IBS demonstrate, for instance, lower pressure in the lower oesophageal sphincter and more oesophageal contraction abnormalities than healthy
Bloating and/or abdominal distension are reported by the vast majority of IBS patients [96]. Even though the underlying mechanisms behind these troublesome symptoms are not entirely known, studies during the last years support the fact that several pathophysiological factors are probably involved. It has also been concluded that mechanisms behind the sensation of abdominal swelling (bloating) versus an actual increase in girth (distension) may differ. By using a washout technique with
Few studies have so far addressed GI secretion in IBS, partly due to methodological problems in assessing secretion. An old study demonstrated that patients with IBS have enhanced intestinal secretion in response to perfused bile acids in the ileum, relative to controls [113]. By simultaneously assessing small intestinal motility (manometry) and chloride secretion (transmucosal potential difference) [114], [115], [116], our group has found an enhanced reactivity of the secretory component of
Since James Ritchie in 1973 demonstrated colonic hyperalgesia by inflating balloons in the sigmoid colon in patients with “the irritable colon syndrome” [118] numerous reports on visceral hypersensitivity in IBS have appeared [100], [119], [120], and rectal hypersensitivity has been proposed to be a biological marker for IBS [119], and useful to discriminate IBS from other GI diseases [121]. However, this has been questioned [122], and importantly visceral hypersensitivity is not present in all
There is strong evidence supporting involvement of altered gastrointestinal motility and secretion, as well as visceral hypersensitivity, in the generation of the hallmark symptoms of IBS. To what extent these alterations depend on alterations in the periphery and/or in the central nervous system, remains unclear, but it seems likely that normalization of these pathophysiological factors could improve symptoms in IBS.
None declared. EGG, electrogastrography; GI, gastrointestinal; HAPC, high-amplitude propagating contraction; IBS, irritable bowel syndrome; MMC, migrating motor complex; SIBO, small intestinal bacterial overgrowth.List of abbreviations