Journal of Gastroenterology

, Volume 47, Issue 11, pp 1177–1185 | Cite as

Altered neuro-endocrine–immune pathways in the irritable bowel syndrome: the top-down and the bottom-up model

  • Cristina Stasi
  • Massimo Rosselli
  • Massimo Bellini
  • Giacomo Laffi
  • Stefano Milani


The interaction between the brain and the gut as a pathological mechanism of functional gastrointestinal disorders has been recently recognized in the pathophysiology of the irritable bowel syndrome. Communication between central nervous system and enteric nervous system is two-directional: the brain can influence the function of the enteric nervous system and the gut can influence the brain via vagal and sympathetic afferents. In patients with irritable bowel syndrome, symptoms may be caused by alterations either primarily in the central nervous system (top-down model), or in the gut (bottom-up model), or in a combination of both. The brain–gut axis may be stimulated by various stressors either directed to the central nervous system (exteroreceptive stress) or to the gut (interoceptive stress). Particularly, clinical evidence suggest that in complex and multifactorial diseases such as irritable bowel syndrome, psychological disorders represent significant factors in the pathogenesis and course of the syndrome. Neuroimaging techniques have shown functional differences between central process in healthy subjects and patients with irritable bowel syndrome. Moreover, a high prevalence of psychological/psychiatric disorders have been reported in IBS patients compared to controls. Several data also suggest an alteration of neuro-endocrine and autonomic output to the periphery in these patients. This review will examine and discuss the complex interplay of neuro-endocrine–immune pathways, closely associated with neuropsychiatric disorders.


Stress Corticotropin releasing hormone Mast cells Exteroreceptive stress Interoceptive stress 



Hypothalamic–pituitary–adrenal axis


Hypothalamic–autonomic nervous system axis


Irritable bowel syndrome


Paraventricular nucleus


Anterior cingulated cortex


Central nervous system


Post-traumatic stress disorder


Emotional motor system




Corticotropin-releasing hormone


Neuropeptide Y


Adrenocorticotropic hormone


Mineralocorticoid receptor


Glucocorticoid receptor


Diarrhea-predominant IBS


Enterochromaffin cell


Constipation-predominant IBS



The authors thank Mrs. Susan Seeley for her help in editing the manuscript.

Conflict of interest

The authors have no conflicts of interest to disclose.


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Copyright information

© Springer 2012

Authors and Affiliations

  • Cristina Stasi
    • 1
  • Massimo Rosselli
    • 1
  • Massimo Bellini
    • 2
  • Giacomo Laffi
    • 1
  • Stefano Milani
    • 3
  1. 1.Dipartimento di Medicina InternaUniversity of FlorenceFlorenceItaly
  2. 2.Unit of Gastroenterology, Department of Internal MedicineUniversity of PisaPisaItaly
  3. 3.Department of Clinical PathophysiologyUniversity of FlorenceFlorenceItaly

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