What is in the future for irritable bowel syndrome (IBS)?

The future of IBS depends on our increasing knowledge of the processes (mechanisms) that cause IBS. Acquiring this knowledge, in turn, depends on research funding. Because of the difficulties in conducting research in IBS, this knowledge will not come quickly. Until we have an understanding of the mechanisms of IBS, newer treatments will be based on our developing understanding of the normal control of gastrointestinal function, which is proceeding more rapidly. Specifically, there is intense interest in intestinal neurotransmitters, which are chemicals that the nerves of the intestine use to communicate with each other. The interactions of these neurotransmitters are responsible for adjusting (modulating) the functions of the intestines, such as contraction of muscles and secretion of fluid and mucus.

5-hydroxytriptamine (5-HT or serotonin) is a neurotransmitter that stimulates several different receptors on nerves in the intestine, including one called the 5-HT4 receptor. Stimulation of these receptors by 5-HT increases muscle contractions in the colon. An example of an experimental drug that affects intestinal neurotransmission is tegaserod. This drug mimics the effect of 5-HT on the 5-HT4 receptor. Thus, because it increases intestinal muscle contractions, tegaserod is being tested for effectiveness in treating constipation-predominant IBS as well as constipation in general.

Another drug that affects neurotransmission is ondansetron. This drug blocks a different receptor, the 5-HT3 receptor, and thereby reduces colonic contractions. Thus, ondansetron (Zofran) has been effective in treating diarrhea-predominant IBS in initial studies. There are drugs that stimulate another receptor, the 5-HT1 receptor. Examples of this type of drug are sumatriptan (Imitrex) and buspirone. These drugs are believed to reduce the responsiveness (sensitivity) of the sensory nerves to what's happening in the intestine. The 5-HT1 receptor stimulators, however, have not yet been tested for effectiveness in IBS. In preliminary studies, fedotozine has been shown to improve functional gastrointestinal symptoms. The mechanism of action of fedotozine is not known, but it also may act by reducing the sensitivity of the sensory nerves.

Finally, there is the issue of a relationship between IBS and intestinal bacteria. Over the next few years, much information will accumulate on this potential relationship.

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What is a reasonable approach to irritable bowel syndrome (IBS)?

The initial approach to IBS-treatment or testing--depends on the patient's symptoms and their duration. If the symptoms clearly fit the definition for IBS and have been present for several years without change, then there is less need for extensive testing to exclude other intestinal and non-intestinal diseases. Rather, treatment that is directed at specific symptoms, as discussed previously, can begin. The role of antibiotics and/or probiotics is currently being studied.

On the other hand, if the symptoms are of recent onset (such as weeks or months), progressively worsening, severe, or associated with "warning" signs, then early testing is appropriate. Warning signs include loss of weight, nighttime awakening, rectal bleeding, and signs of inflammation, such as fever or abdominal tenderness. Testing also is appropriate if, in addition to the symptoms of IBS, there are other prominent symptoms that are not part of IBS (for example, abdominal distention, increased flatus, or vomiting). Finally, testing is warranted if attempts at treating the symptoms of IBS are unsuccessful.

If there are symptoms that suggest non-IBS diseases, tests that are specific for these conditions should be done first. The reason is that if these other tests disclose disease other than IBS, it may not be necessary to do additional testing. Examples of symptoms and possible testing include:

  •     Vomiting: upper gastrointestinal endoscopy to diagnose inflammatory or obstructing diseases; and gastric emptying studies and/or electrogastrography to diagnose impaired emptying of the stomach.
  •     Abdominal distention with or without increased flatulence: upper gastrointestinal and small intestinal X-rays to diagnose obstructing diseases; and hydrogen breath testing to diagnose SIBO.
  •     Constipation without pain: colonoscopy or barium enema to exclude colonic cancer; marker studies to diagnose slow colonic transit; and ano-rectal motility studies to diagnose rectal muscle disorders

For a patient with typical symptoms of IBS who requires testing to exclude other diseases, the testing might reasonably include a standard screening panel of blood tests and stool specimens for examination for parasites, pus, and blood. A plain X-ray of the abdomen may be done during an episode of abdominal pain (to look for intestinal blockage or obstruction). Testing for lactose intolerance or a trial of a strict lactose-free diet should be done. Colonoscopy (and, possibly, esophago-gastro-duodenoscopy, or EGD) would be the next test, probably with multiple biopsies of the colon (and stomach and duodenum if EGD is done). Finally, small intestinal X-rays might be done.

If all of the above appropriate testing reveals no disease that could be causing the symptoms, other tests should be considered. These tests include hydrogen breath testing to diagnose SIBO and antro-duodenal and colonic motility studies to diagnose intestinal muscle or nerve disorders. These studies probably should be done at centers that have experience and expertise in diagnosing and treating these diseases.

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