Enteroendocrine and neuronal mechanisms in pathophysiology of acute infectious diarrhea

Michael Camilleri, Sara Nullens, Tyler Nelsen

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


Background: While enterocyte secretion is the predominant mechanism considered responsible for secretory diarrhea in response to acute enteric infections, there are several lines of evidence that support alternative mechanisms controlling fluid and electrolyte secretion in diarrhea. Aim: To review enteroendocrine and neuronal mechanisms that participate in the development of acute infectious diarrhea. Recent Advances: Acute infectious diarrheas due to bacterial toxins (e.g., cholera, E. coli heat-stable enterotoxin, C. difficile) and rotavirus are all associated with secretion of transmitters from enteroendocrine cells (e.g., 5-HT) and activation of afferent neurons that stimulate submucosal secretomotor neurons. The latter secrete acetylcholine (which binds to muscarinic receptors on epithelial cells) and VIP. Involvement of nerves was demonstrated by inhibition of bacterial toxin-induced secretion by hexamethonium (nicotinic), tetrodotoxin (Na + channel blocker), and lidocaine (visceral/mucosal afferents). Nicotinic receptors are present on secretomotoneurons and these are activated by release of acetylcholine from enteric interneurons or extrinsic efferent fibers. Specific organisms also modify other mechanisms that may contribute to development of acute diarrhea. Thus, mucin secretion, activation of motor mechanisms, increased mucosal permeability and inhibition of bile acid absorption have been reported in specific types of acute infectious diarrhea. Conclusion: New therapies targeting neural and transmitter mediation including 5-HT, VIP, NPY, as well as toxin receptors and channels activated during acute infectious diarrhea could usher in a novel approach to enhancing glucose-electrolyte solutions used in the treatment of acute diarrhea.

Original languageEnglish (US)
Pages (from-to)19-27
Number of pages9
JournalDigestive diseases and sciences
Issue number1
StatePublished - Jan 2012


  • CFTR
  • Channel
  • Chloride
  • Cholera
  • Goblet cell
  • Guanylin

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology


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