A new study published in the Gastrointestinal and Liver Physiology discussed that secretory diarrhea evidences a disbalance in the intestinal absorptive and secretory processes. Here, the rampant fluid secretion––which is regulated by chloride ion secretion––surpasses the absorptive capacity of the intestinal epithelium, causing copious amounts of water loss through stools.

Secretory diarrheas often have an infectious etiology and could be precipitated by various pathogens, for instance – certain bacteria or viruses. Allergens, drug intolerance, and intrinsic disruptions in bile acid homeostasis can also contribute to the pathogenesis of secretory diarrhea.

The present paper presented an overview of the cellular and molecular mechanisms of the regulatory mechanisms by which Cl− and fluid secretion are regulated, thereby, their dysregulation in diarrheas and the contemporary and newer therapeutic approaches. Further, novel modalities of constipation management that exploit intestinal secretory mechanisms to render the stools more fluid were also discussed.

Moreover, irrespective of the etiology, the regulation of transport proteins plays the primary role in secretory diarrhea, like the chloride-ion secretory mechanism. Recent research has gained an in-depth understanding of these processes and the intra- and extra-cellular influences. These discoveries are advantageous for devising targeted therapies. 

Diarrhea is a major cause of mortality and morbidity among pediatric populations – under five years of age. Recurrent diarrhea in infants and children has also been associated with long-lasting cognitive side effects. Small molecule inhibitors targeting the chloride-ion secretory pathways have been found to be efficacious in treating diarrhea emerging from an array of etiologies.  

Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2022 Apr 1;322(4):G405-G420. doi: 10.1152/ajpgi.00316.2021.