Despite its high prevalence, considerable impairment of health related quality of life (HRQoL), and burden of illness [1
], the available treatment options for IBS are limited and effective therapy remains a challenge to clinicians. IBS as defined by current criteria is likely to be a heterogeneous disorder with a core group of patients having a generalized brain gut disorder, while smaller subgroups may have similar symptoms arising from celiac disease, microscopic colitis or bacterial overgrowth. In the majority of patients, IBS symptoms result from a complex dysregulation of the brain gut axis, involving variable contributions of peripheral, spinal and supraspinal abnormalities [2
]. Alterations in gastrointestinal motility have been identified in some patients, and together with alterations in intestinal fluid handling, may play an important role underlying IBS-related bowel habit irregularities. Enhanced perception of signals arising from the gastrointestinal (GI) tract (“visceral hypersensitivity”) is considered a key factor underlying abdominal pain and discomfort [4
]. Considerable preclinical and clinical evidence supports the presence of altered central arousal/stress circuits which may play a key role in central pain amplification, and in frequently associated symptoms of anxiety [5
]. Recent evidence implicates a possible alteration in host microbial interactions and in mucosal neuroendocrine immune interactions [6
]. Despite the initial enthusiasm about potentially novel treatment approaches, it remains to be determined which of the various reported abnormalities truly contribute to IBS symptoms, to health care seeking and to HRQoL impairment, which targets are relevant for drug development, and which of the growing list of abnormalities represent secondary effects or epiphenomena.