Irritable bowel syndrome, with its symptoms of intense contractions of the colon and hypersensitivity to painful stimuli, was once thought to be a psychosomatic condition. Now its biological origins are becoming clearer and the finger of suspicion is pointing at digestive enzymes that have also been linked to inflammatory bowel disease.

Researchers at the University of Calgary in Alberta, Canada, extracted fluid from the colonic tissue of 18 people with irritable bowel syndrome and injected it into the large intestines and paws of mice. The fluid stimulated nerve cells in the animals’ guts and paw, reproducing the symptoms of the condition.

Fluid from healthy people did not provoke these reactions. The researchers also found that the activity of serine proteases in the colonic tissue of irritable bowel patients was double that of fluid from the healthy group. These enzymes break down the peptide bonds in proteins, helping to digest food or prevent infection. They are produced by the body but also by bacteria and protozoa in the gut.

Irritable bowel patients are often classified according to whether they experience diarrhea, constipation or both, but the researchers found the same high levels of protease activity across the entire group. “For the first time, the same mediator was found in all [irritable bowel syndrome] patients, that was a surprise to us”.

Another surprise was that raised protease activity was also found in people with inflammatory bowel disease (Journal of Clinical Investigation). Serine proteases activate a receptor called PAR2 which is found on nerve cells, epithelial cells and smooth muscle cells. If these cells are over stimulated in irritable bowel patients, it may explain why they complain of widespread pain and hypersensitivity as well as abdominal symptoms.

Determining the source of the protease activity could lead to better treatments. Important questions remain, including the exact molecular identity of the protease, where it comes from, and how it gets to be released at higher levels,” said Lars Eckmann at the University of California, San Diego.

Previous studies have linked high numbers of mycobacteria in the gut flora to inflammatory bowel disease, and a protozoan like an organism called blastocystis to irritable bowel syndrome. It is not clear, however, whether these organisms are a cause of the symptoms or an incidental finding.

Australian Doctor, The Best of New Scientist, (Special Issue)

Share This