Peripheral factors in the pathophysiology of irritable bowel syndrome

Abstract

The pathophysiology of IBS is complex and still incompletely known. Both central and peripheral factors are thought to contribute to the symptoms of IBS, including psychosocial factors, abnormal GI motility and secretion, and visceral hypersensitivity. In this review the involvement of peripheral factors in the pathophysiology in IBS is reviewed. Altered GI motility is commonly found in this patient group, even though a specific motor pattern has been hard to find. Colonic transit has been found to be of relevance for the bowel habit of the patient. Abnormal gas handling within the gut is also commonly seen, and seems to be one, but not the only factor responsive for bloating. There is also limited evidence supporting the presence of abnormal GI secretion in IBS, but its relevance for symptoms remains unclear. Visceral hypersensitivity is currently considered to be one of the most important pathophysiological factors in IBS. It can be modulated by several external and internal factors and recent studies support an association between colorectal sensitivity and the symptoms reported by the patients, especially pain.

Introduction

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.