COMMENTARY

We May Be Able to Stop Common Lethal Secretory Diarrhea by Activating the Intestinal Calcium Sensing Receptors

John Geibel, MD, DSc

Disclosures

January 12, 2007

 

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Acute diarrheal illness occurs following ingestion of food or water contaminated by bacteria-producing toxins or the toxins themselves. Following ingestion, there is a rapid increase in secretion of salt and water from the intestines which, if left unchecked, often results in vascular collapse and death. Infants, the elderly, and debilitated individuals are especially vulnerable. Secretory diarrhea is the world's number 1 killer of children under 5 years of age. Two major types of acute and severe diarrhea are: (1) cholera - caused by vibrio cholera, which produces cholera toxin, and (2) travelers' or infantile diarrhea, caused by STa toxin from toxigenic Escherichia coli.

Cholera typically results from contamination of food and water following natural disasters.[1,2] Travelers' diarrhea is primarily associated with traveling in areas with less developed sanitation.

Many therapies have been used to combat this problem, with mixed results. Mortality still remains high, with deaths from acute diarrheal illnesses in the millions each year.

Our research group has recently published a novel and unique approach[3] showing that activation of a specific surface receptor in cells lining the intestine can stop the fluid secretion caused by cholera and STa toxins. Activating the calcium sensing receptor by raising the calcium concentration in the delivered fluid, or adding specific receptor activators to the fluid which bathes the intestine, was effective in halting toxin-induced fluid secretion in animals. Activating this receptor halts fluid secretion by increasing the destruction of cell-signaling molecules that are activated by the bacterial toxins. Use of specific agents to activate this receptor in the intestine may provide a potent new means for treating life-threatening secretory diarrheas. It is now time to learn whether this intervention will also work in humans.

That's my opinion. I'm Dr. John Geibel, Professor of Surgery at Yale and a member of the eMedicine Editorial Board.

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