Enteroendocrine and Neuronal Mechanisms in Pathophysiology of Acute Infectious Diarrhea

Abstract

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.

Complex Interactions Among Diet, Gastrointestinal Transit, and Gut Microbiota in Humanized Mice

“…31 In infectious diarrhea, such as rotavirus and cholera, the role of serotonin signaling in the pathogenesis of diarrhea has been well described. 32 This study implicates the possible involvement of the serotonin pathway in the diet-induced alterations in GI transit time, a result of signaling by commensal gut bacteria. However, given the close interrelationship of diet, transit time, and microbiota, further studies that leverage a variety of experimental tools, including genetic models of host and resident microbes, will be required to better understand the role of specific pathways and molecules (eg, serotonin) in mediating these interactions.…”

Microbiota and host determinants of behavioural phenotype in maternally separated mice

“…This measure has been previously reported as a parameter of stress-induced stimulation of the colon by sacral parasympathetic outflow 28 . Acetylcholine is the main excitatory neurotransmitter in the mammalian enteric nervous system and plays an important role in the control of digestive functions 56,57 , gut motility 58 and permeability 15 . Our data thus suggest that MS leads to increased activity of cholinergic nerves in the colon independently of the presence of bacteria.…”

Diarrhetic effect of okadaic acid could be related with its neuronal action: Changes in neuropeptide Y

“…In the gut, NPY inhibits gastrointestinal motility and water and electrolyte secretion, especially ClÀ throughout the entire intestine (Cox, 2007;HolzerPetsche et al, 1991;Hubel and Renquist, 1986;Saria and Beubler, 1985). This behavior has made NPY to be currently investigated as a key molecule for using in anti-diarrheic drugs (Camilleri et al, 2011;Laburthe, 1990;Moriya et al, 2010;Tough et al, 2011;Vona-Davis and McFadden, 2007;Wapnir and Teichberg, 2002).…”