IBS: a syndrome or many diseases?
Patients with irritable bowel syndrome (IBS) are characterized by a broad spectrum of gastrointestinal (GI) symptoms. These IBS-symptoms and symptoms of other functional GI disorders frequently overlap. Moreover, at least in patients with severe disease manifestations there is a remarkable psychiatric comorbidity. There is a number of abnormalities of GI functions including sensory and motor dysfunction that are believed to play a role for the manifestation of symptoms in patients with these functional gastrointestinal disorders (FGID). Family studies provide strong evidence for a clustering of FGID in families. Furthermore, twin studies clearly demonstrate an increased concordance in monocygotic compared to dicygotic twins. This points towards the role of one or more hereditary factors. Considering sensory and motor function as well as the psychiatric comorbidity, polymorphisms of adrenergic, opioidergic or serotonergic receptors as well as G-protein beta3 (GNB3) subunit gene polymorphism and polymorphisms of 5-HT transporter genes are suitable mechanisms for these abnormalities. Hence acute GI infections with a mucosal inflammation appear to trigger a cascade of events that ultimately results in the manifestation of FGID, it is reasonable to assume that functionally relevant polymorphisms of genes with immunmodulating and/or neuromodulating features (OPRM1, IL-4, IL-4R, TNFalpha) play a role. It has emerged that a number of various factors may contribute to the manifestation of functional GI disorders. The currently symptom based labels for functional GI disorders may be helpful to categorize patients and target therapy. However, various underlying pathophysiologies may cause similar symptom patterns. Thus, it is reasonable to anticipate that IBS will be dissected accordingly and our disease concepts will accept the irritable bowel syndrome as the clinical manifestation of a number of different disorders.
Holtmann
Gerald
G
Department of Gastroenterology, Hepatology and General Internal Medicine, Royal Adelaide Hospital,University of Adelaide, North Terrace, South Australia 5000, Adelaide, Australia. g.holtmann@uni-essen.de
D005767:Gastrointestinal Diseases / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics*
C454420:G-protein beta3 subunit; D020962:Heterotrimeric GTP-Binding Proteins