Role of Brain-Gut Axis in Irritable Bowel Syndrome

抄録

Irritable bowel syndrome (IBS) is characterized by chronic and recurrent abdominal pain associated with abnormal bowel movement but without major organic diseases in routine clinical examinations. Gastrointestinal symptoms in IBS are defined with Rome IV criteria. IBS patients show exaggerated reaction of colonic motility to psychosocial stressors and high prevalence of depressive and/or anxiety disorders. Post-infectious IBS provides evidence of gut microbiota as one of important etiological factors. Basic understanding of communication between gut immune system and neurons/glia as well as increased mucosal permeability is a hallmark of progression of investigation of IBS.

Reciprocal brain-gut interactions underlies fundamental mechanism in the formation of IBS. Brain imaging techniques including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), or viscerosensory evoked potential (VEP) could enable use to detect the mechanism of visceral perception, activated regional brain, functional module of the brain, neurotransmitters/modulators, and patterns of connectivity of the brain regions.

Corticotropin-releasing hormone (CRH) and 5-hydroxytryptamine (5-HT) are the plausible molecules relating brain-gut pathophysiology of IBS. IBS patients showed different distribution of the genetic polymorphism of the CRH receptor-1 genes and CRH receptor-2 genes from healthy subjects. Previous studies clarified that exaggerated function of the amygdala, anterior cingulate cortex, and insula and that impaired function of the dorsolateral prefrontal cortex or medial prefrontal cortex in IBS patients. IBS patients also showed more excitation of the amygdala in response to the exogenous administration of CRH than control subjects. We found that excitability of the medial prefrontal cortex in response to colorectal distention negatively correlated with adrenocorticotropic hormone (ACTH) secretion after the administration of CRH in healthy subjects. By contrast, negative correlation between activity of the medial prefrontal cortex and ACTH secretion to CRH load was disrupted in IBS patients. Efficacy of 5-HT3 antagonists on diarrhea-predominant IBS patients and that of antidepressants on IBS regardless of subtypes also support the important role of 5-HT in IBS.

Novel pharmacotherapy along the clarified mechanism is expected in IBS. Further research on brain-gut interactions in IBS is warranted.