Large volumes of water are normally secreted into the small intestinal lumen, but a large majority of this water is efficienty absorbed before reaching the large intestine. Diarrhea occurs when secretion of water into the intestinal lumen exceeds absorption.
Many millions of people have died of the secretory diarrhea associated with cholera. The responsible organism, Vibrio cholerae, produces cholera toxin, which strongly activates adenylyl cyclase, causing a prolonged increase in intracellular concentration of cyclic AMP within crypt enterocytes. This change results in prolonged opening of the chloride channels that are instrumental in secretion of water from the crypts, allowing uncontrolled secretion of water. Additionally, cholera toxin affects the enteric nervous system, resulting in an independent stimulus of secretion.
Exposure to toxins from several other types of bacteria (e.g. E. coli heat-labile toxin) induce the same series of steps and massive secretory diarrhea that is often lethal unless the person or animal is aggressively treated to maintain hydration.