Irritable bowel syndrome, or IBS, is a common gastrointestinal syndrome that may affect up to 15% of the population in the U.S. The primary symptom of IBS is abdominal discomfort that is associated with either an alteration in bowel habit (diarrhea, constipation, or diarrhea alternating with constipation) or that is improved with a bowel movement. In fact, the alteration in bowel habit is used to subgroup patients into three clinically separate groups. It is not certain if the cause (etiology) is the same for all groups or if each group has a distinct and separate cause. Various theories regarding the causes of IBS include:
- abnormalities of the function of the intestinal muscles or their controlling nerves,
- abnormal intestinal neural sensation,
- altered immunology of the intestine,
- intestinal inflammation, and
- alteration or overgrowth of the bacteria that colonize the intestine.
The last of these potential causes (etiologies) - bacterial alteration or overgrowth - has been explored in an important scientific study recently published in the New England Journal of Medicine by Pimentel et al. In this study, the authors randomized over 1,000 patients with IBS not associated with predominant constipation (i.e., they had mostly normal and/or diarrheal bowel habits) to receive either an antibiotic, rifaximin (Xifaxan), or a placebo (an inactive pill) for two weeks. The patients were followed during treatment and for up to 10 weeks after completing treatment to assess the effects of treatment on their symptoms. With respect to symptoms, the patients receiving rifaximin did better than the patients receiving placebo, and the difference was statistically significant.
The implications of the study are two-fold: first, rifaximin s effective in the treatment of IBS, and second, since rifaximin is an antibiotic and presumably works by affecting the intestinal bacteria, it suggests that bacteria may have a role in causing IBS, at least IBS not associated predominantly with constipation. Both of these implications need to be examined.
The study leaves little doubt that rifaximin is effective in treating patients with irritable bowel syndrome. It is important, however, to look at the magnitude of the effectiveness of rifaximin (as compared with placebo).
Symptoms of IBS frequently respond to placebo. Thus, in the study by Pimentel, 31% of the patients receiving placebo improved. On the other hand, 41% of the patients receiving rifaximin improved. The difference in response between placebo and rifaximin was only 10%. Therefore, it can be stated with certainty only that a small proportion of patients with IBS - 10% - were helped by rifaximin.
Why was rifaximin effective in such a small proportion of patients with IBS? There are two potential explanations. The first is that bacterial alteration or overgrowth - presumably what was being treated by rifaximin - is, in fact, the cause of IBS in only a small proportion of patients. The second is that the criteria used for including patients for study did not well for select patients who had bacterial alteration or overgrowth as the cause of their symptoms. Perhaps, one should not be using the existing criteria for IBS to select patients for treatment with rifaximin, and perhaps additional criteria should be used. Pimentel et al. used the Rome II criteria for diagnosing and selecting patients, and the most important criterion of Rome II are abdominal discomfort associated with an alteration in the bowel habit or relieved by a bowel movement. But Pimentel also used abdominal bloating to select patients, which is interesting because bloating is not one of the criteria for diagnosing IBS.
Intestinal bacteria may cause abdominal discomfort accompanied with a change in bowel habits or relieved by a bowel movement, but the symptoms that bacteria in the intestine commonly cause are diarrhea and abdominal bloating (or distention) due to intestinal gas that the bacteria produce. Perhaps if patients had been selected more for diarrhea and intestinal gas (i.e., abdominal bloating or distention) and less for abdominal discomfort, the proportion of patients responding to rifaximin might have been greater. In other words, the typical symptoms of IBS - abdominal discomfort associated with an alteration in bowel habit or relieved by a bowel movement - may not be the criterion for selecting patients for treatment with rifaximin. It is possible that rifaximin can help a larger number of patients if criteria other than the one used for diagnosing IBS are employed to select patients for treatment.
But if the criteria for IBS are not good for selecting patients, is rifaximin (Xifaxan) really a good treatment for IBS or is it instead a good treatment for another gastrointestinal condition whose symptoms overlap with IBS?
Quick GuideIBS - Irritable Bowel Syndrome: Symptoms, Diet, Treatment
REFERENCE: Pimentel et al. Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation. N Engl J Med 2011;364:22-32.