Evolving Concepts of the pathogenesis of irritable bowel syndrome: To treat the brain or the gut?

Recent in-depth studies of irritable bowel syndrome (IBS) that assessed multiple physiological endpoints in large patient cohorts confirm evidence of abnormal motility, sensation, and psychosocial disturbances. However, the proportion with hypersensitivity has dropped from the time of the original claim that it is a "biological marker" of IBS. Discomfort thresholds in male and female IBS patients normalize over time, whereas IBS symptoms persist, and increased colonic sensitivity in IBS is strongly influenced by a psychological tendency to report pain and urge rather than increased neurosensory sensitivity. The objectives of this article are to review the classical pathophysiology of IBS, the putative roles of infection, inflammation, and bacterial flora; consider mimics of IBS; assess the evidence that IBS is a serotonergic disease; evaluate recent advances in membrane biology and neuroscience related to IBS; consider genetic association with IBS and its endophenotype; and discuss whether to treat the gut or the brain.