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Gene, environment, and brain-gut interactions in irritable bowel syndrome


  • This paper was presented at the Asian Pacific Topic Conference on Functional Gastrointestinal Disorders, November 27 (Sat), 2010, Tokyo, Japan.

  • Grant Support: This research was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan, and a Grant-in-Aid for Scientific Research from the Ministry of Health, Welfare, and Labor of Japan.

Professor Shin Fukudo, Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai 980-8575, Japan. Email:


The genetic predisposition and influence of environment may underlie in the pathogenesis and/or pathophysiology of irritable bowel syndrome (IBS). This phenomenon, gene x environment interaction together with brain-gut interactions is emerging area to be clarified in IBS research. Earlier studies focused on candidate genes of neurotransmitters, cytokines, and growth factors. Among them, some studies but not all studies revealed association between phenotypes of IBS and 5-hydroxytryptamine (5-HT)-related genes, noradrenaline-related genes, and cytokine genes. Recent prospective cohort study showed that genes encoding immune and adhesion molecules were associated with post-infectious etiology of IBS. Psychosocial stressors and intraluminal facotrs especially microrbiota are keys to develop IBS. IBS patients may have abnormal gut microbiota as well as increased organic acids. IBS is disorder that relates to brain-gut interactions, emotional dysregulation, and illness behaviors. Brain imaging with or without combination of visceral stimulation enables us to depict the detailed information of brain-gut interactions. In IBS patients, thalamus, insula, anterior cingulate cortex, amygdala, and brainstem were more activated in response to visceral stimulation than controls. Corticotropin-releasing hormone and 5-HT are the candidate substances which regulate exaggerated brain-gut response. In conclusion, gene x environment interaction together with brain-gut interactions may play crucial roles in IBS development. Further fundamental research on this issue is warranted.