What is the role of the brain-gut axis in the pathophysiology of irritable bowel syndrome (IBS)?

Updated: Dec 30, 2019
  • Author: Mohammad F El-Baba, MD; Chief Editor: Carmen Cuffari, MD  more...
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The brain-gut axis is a bidirectional pathway that links higher cortical centers with visceral afferent sensation and intestinal motor function. Regulation of these connections occurs via numerous neurotransmitters found in the brain and gut, including cholecystokinin, vasoactive intestinal peptide, substance P, serotonin (5-hydroxytryptamine [5-HT]), and many others. These transmitters act at different sites in the brain and gut and lead to varied effects on gastrointestinal motility, pain control, emotional behavior, and immunity.

Serotonin plays a critical role in the regulation of GI motility, secretion, and sensation. In the GI tract, 5-HT is synthesized by the enterochromaffin cells (EC) located within the mucosa of the intestine. 5-HT released by EC cells initiates peristaltic and secretory reflexes by acting on its receptors. Several subclasses of 5-HT receptors are differentiated on the basis of structure, molecular mechanism, and function. Excess serotonin is removed by the serotonin transporter (SERT) expressed by intestinal epithelial cells. Studies have shown that irritable bowel syndrome symptoms may be related to imbalance in mucosal 5-HT availability caused by defects in 5-HT production, serotonin receptors, or SERT.

Dysregulation of the brain-gut system is becoming an acceptable theory to explain the functional GI disorders. Furthermore, several studies have hypothesized that specific 5-HT receptor antagonists may be beneficial in irritable bowel syndrome. Numerous newer noninvasive imaging techniques (eg, positron emission tomography, functional MRI) have been applied to assess brain-gut interactions in healthy patients and in those with irritable bowel syndrome.

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