Pathophysiology of irritable bowel syndrome

Despite the continued absence of a definitive biomarker for irritable bowel syndrome (IBS), research over the last three decades has identified a wide range of underlying pathophysiological abnormalities. Peripheral mechanisms include gastrointestinal infection, changes in the gut microbiome, visceral hypersensitivity, increased intestinal permeability, low-grade mucosal inflammation and altered immune function, abnormal gastrointestinal motility, and the role of serotonin, bile acid metabolism, and carbohydrate metabolism. Central mechanisms include psychological health and altered central pain processing. These central and peripheral mechanisms can act in an integrated way to cause IBS symptoms, via the gut-brain axis, supporting the concept of IBS as a disorder of gut-brain interaction. Some mechanisms can be quantified using validated tests and questionnaires, including abnormal bile acid metabolism, accelerated colonic transit, and psychological comorbidity. However, more work is needed to translate most mechanisms into reliable tests able to identify specific targets for treatment. This Review discusses the current understanding of the pathophysiology of IBS in terms of peripheral, central, and integrated mechanisms.