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

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Abstract

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.

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Abbreviations

HPA:

Hypothalamic–pituitary–adrenal axis

HANS:

Hypothalamic–autonomic nervous system axis

IBS:

Irritable bowel syndrome

PVN:

Paraventricular nucleus

ACC:

Anterior cingulated cortex

CNS:

Central nervous system

PTSD:

Post-traumatic stress disorder

EMS:

Emotional motor system

GC:

Glucocorticoid

CRH:

Corticotropin-releasing hormone

NY:

Neuropeptide Y

ACTH:

Adrenocorticotropic hormone

MR:

Mineralocorticoid receptor

GR:

Glucocorticoid receptor

D-IBS:

Diarrhea-predominant IBS

EC:

Enterochromaffin cell

C-IBS:

Constipation-predominant IBS

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

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The authors have no conflicts of interest to disclose.

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Stasi, C., Rosselli, M., Bellini, M. et al. Altered neuro-endocrine–immune pathways in the irritable bowel syndrome: the top-down and the bottom-up model. J Gastroenterol 47, 1177–1185 (2012). https://doi.org/10.1007/s00535-012-0627-7

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