Stopping Diarrhea Caused by Bacteria

John Geibel, M.D. and
Steven Hebert, M.D.

Turning on a surface receptor in cells lining the intestinal wall can halt the often deadly diarrhea brought on by the bacteria V. cholera and E. coli, according to a Yale School of Medicine study published May 15 in the Proceedings of the National Academy of Sciences.

Secretory diarrhea, which occurs when the small and large intestine secrete salt and water at rates higher than the intestine can reabsorb, is a major killer of children under five years of age worldwide. Unless stopped, the diarrhea can rapidly produce massive losses of fluid and salt and result in heart failure.

“Despite new therapies, mortality from acute diarrheal illnesses remains in the millions each year,” said authors Steven Hebert, M.D., professor and chair of the Department of Cellular and Molecular Physiology, and John Geibel, M.D., professor in the Department of Surgery. “Development of specific agents to target this intestinal receptor could provide a new approach for treating this debilitating and life threatening diarrhea.”

The acute diarrhea associated with infantile diarrhea, cholera or foreign travel is a result of eating food or drinking water contaminated with bacteria. The bacteria produce a toxin that over stimulates the intestinal cell’s normal secretory machinery. Outbreaks of cholera from contaminated food and water are often seen following earthquakes, tsunamis, floods and typhoons/hurricanes. Travelers’ diarrhea, which is caused by the toxin STa, can affect individuals traveling to areas with less highly developed hygiene and sanitation.

Hebert, Geibel and colleagues found that activating a calcium/nutrient sensing receptor in the intestinal lining stopped the fluid secretions caused by cholera and STa toxins. They report that activation of the receptor halts fluid secretion by increasing the destruction of cell signaling molecules that are activated by the bacterial toxins.

The receptor detects changes in calcium and other nutrients like amino acids in the fluid bathing the exterior of cells. The investigators tried raising the calcium level and adding specific receptor activators to the fluid bathing the intestines. Both methods were effective in halting toxin-induced fluid secretion in animals.

PNAS: (May 15, 2006)

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