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 another condition called inflammatory bowel disease.
Nathalie Vergnolle at the University of Calgary in Alberta, Canada, and her colleagues extracted fluid from colonic tissue taken from 18 people with IBS and injected it into the large intestines and paws of mice. The fluid stimulated nerve cells in the animals鈥� guts and paws, reproducing the symptoms of IBS. Fluid from healthy people did not provoke these reactions.
They also found that in the fluid from IBS patients, the activity of enzymes called serine proteases was double that of fluid from the healthy group. These enzymes break down the peptide bonds in proteins, helping to digest food or protect us from infection. They are produced by the body, but also by bacteria and protozoa in the gut.
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IBS patients are often classified according to whether they experience diarrhoea, constipation or both, but Vergnolle found the same high levels of protease activity across the entire IBS group. 鈥淔or the first time, the same mediator was found in all IBS patients,鈥� she says. 鈥淭hat was a surprise to us.鈥� Another surprise was that raised protease activity was also found in people with inflammatory bowel disease (IBD) 鈥� a more serious condition that can require surgery (Journal of Clinical Investigation, ).
Serine proteases activate a receptor called PAR2, which is found throughout the body on nerve cells, epithelial cells and smooth muscle cells. If these cells are being overstimulated in IBS patients, it may explain why they complain of widespread pain and hypersensitivity as well as abdominal symptoms.
鈥淚t may explain why people with IBS complain of widespread pain and hypersensitivity rather than just abdominal symptoms鈥�
Determining the source of the protease activity could one day lead to better treatments. 鈥淚mportant questions remain, including the exact molecular identity of the protease, where it comes from, and how it gets to be released at higher levels,鈥� says Lars Eckmann at the University of California, San Diego.
Previous studies have linked high numbers of mycobacteria in the gut flora to IBD, and a protozoon-like organism called Blastocystis to IBS. It is not clear, however, whether these organisms are a cause of the symptoms or an incidental effect. A protease inhibitor has already been trialled in Japan as a treatment for IBD, with promising results.
