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General introduction 9 1 General introduction Irritable bowel syndrome Irritable bowel syndrome (IBS) is a highly prevalent disorder of brain-gut-interaction that is characterized by recurrent abdominal pain in combination with alterations in bowel habits. 3 Based on predominant stool pattern, IBS can be subtyped as diarrhea- predominant (IBS-D), constipation-predominant (IBS-C), mixed type (IBS-M), or unclassified IBS (IBS-U). Besides abdominal pain and disturbed defecation, many patients experience additional gastrointestinal (GI) symptoms such as abdominal cramping 4 , bloating (subjective sensation of abdominal fullness) and/or distention (objective increase in abdominal girth) 5,6 , flatulence 7 , and dyspepsia. 8 Symptoms are known to occur in episodes 9 with a chronic relapse remitting nature and vary widely between as well as within subjects, reflecting the complex, heterogeneous and multifactorial phenotype of IBS. 10 IBS is part of a spectrum of functional GI disorders (FGID), ‘ classified by GI symptoms related to any combination of the following: motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system (CNS) processing’ , in absence of an identifiable organic cause. Other FGIDs include, but are not limited to functional heartburn, functional dyspepsia, belching, and functional constipation. 11 IBS often overlaps with these FGIDs 12-16 and is likely to have, at least to some extent, common underlying etiological mechanisms. In addition, IBS is also associated with various other intestinal, extra-intestinal, and psychiatric conditions, e.g. gastro-intestinal reflux disease (GERD), pelvic floor dyssynergia, chronic fatigue syndrome 17 , overactive bladder, fibromyalgia, increased somatization, depression, and anxiety. 18 Symptom-based diagnosis At present, specific biomarkers to confirm IBS are not available and a diagnosis is made based on presence of typical symptoms. 19,20 Alarm symptoms that may require further investigations before diagnosing a patient with IBS are presented in Box 1.1 .