HONOLULU — Modification of the gut flora is emerging as a promising new treatment approach for the common and vexing problem of irritable bowel syndrome.
Two therapeutic strategies are being pursued. One entails adding bacteria to the gut in the form of oral probiotics. The other involves selectively subtracting bacteria from the gut flora with a non-systemically absorbable antibiotic. Evidence that both approaches alter irritable bowel syndrome (IBS) pathology and modulate symptoms was presented at the annual meeting of the American College of Gastroenterology.
The gut flora has been called “the forgotten organ.” But that's changing, said Dr. Eamonn M.M. Quigley, professor of medicine at of the National University of Ireland, Cork. He presented a full IBS spectrum from diarrhea to the constipation-predominant subtype.
The probiotic resulted in a double-blind trial involving 165 women with IBS randomized to 4 weeks of daily capsules containing the novel probiotic bacterium Bifidobacteria infantis 35624 or placebo. Baseline bowel movement (BM) frequency ranged across the significant improvement in BM frequency, concentrated among patients at either end of the frequency distribution. Women with constipation—those in the bottom 15th percentile in terms of baseline BM frequency—experienced a significant increase in frequency that brought them within the 1–2 movements per day range defined by investigators as normal. In contrast, patients with diarrhea as defined by a BM frequency in the 81st percentile or above experienced a significant decrease in frequency to within normal range.
The probiotic resulted in a net 23% improvement over placebo in terms of IBS symptom scores across the entire study population. Patients in the middle range of baseline BM frequency experienced no significant change with the probiotic compared with placebo.
A composite score based on abdominal pain, bloating, and bowel habit satisfaction was significantly improved with probiotic therapy over placebo in patients with diarrhea-predominant IBS, showed a strong but not statistically significant favorable trend in the smaller group of women with constipation-predominant IBS, and no change in alternator-type patients. There were no probiotic-related side effects. The improved stool function and other benefits of B. infantis 35624 lasted 1–3 weeks after treatment discontinuation, the gastroenterologist added.
Dr. Quigley stressed that not all probiotics are alike. They're not classified as drugs, so they're prone to the same quality-control issues that arise with other health food-type products. The most clinically effective of them—as he and others have shown true for B. infantis 35624 in animal studies—have the ability to not only modify the gut flora, but more importantly to modulate immune activity between the flora and gut mucosa.
Dr. Mark Pimentel presented a double-blind trial in which 87 patients with all types of IBS were randomized to the nonabsorbable antibiotic rifaximin (Xifaxan) at 400 mg t.i.d. or placebo for 10 days. Of patients in the rifaximin group, 38% were deemed clinical responders based upon a greater than 50% improvement in global symptom scores, compared with 16% of those on placebo. The improvement was durable, lasting for roughly 2 months following just 10 days of treatment.
The clinical response rate was greater in patients with diarrhea-predominant IBS: 49%, compared with 23% with placebo. Bloating was also significantly improved. Constipation was not, although the number of affected patients was too small to draw definitive conclusions, according to Dr. Pimentel, director of the gastrointestinal motility program at Cedars-Sinai Medical Center, Los Angeles.
Prior studies suggest that many IBS patients have small bowel overgrowth of hydrogen or methane-producing bacteria. In the current study, the presence and extent of methane production on a lactulose breath test correlated strongly with constipation severity. This suggests that knocking out methane-producing bacteria in the small bowel may be a good therapeutic strategy in patients with constipation-predominant IBS, he added.
Session cochair Dr. Nicholas J. Talley said he doesn't think probiotics or antibiotics are ready for prime-time use in IBS; it's still unclear how common small bowel bacterial overgrowth is in IBS. Also, the gut flora is very well adjusted. “It's there with you for life. It doesn't want to go. If you change it, you have to keep changing it. So this is going to be maintenance therapy, not on-off antibiotic therapy. And I'm never going to be able to recommend antibiotics every 2 weeks to my patients for the rest of their lives. That's just not safe or practical, no matter what you use,” said Dr. Talley, professor of medicine at the Mayo Medical School, Rochester, Minn. In contrast, there is now general agreement that probiotic therapy is safe for the patient and community. It is being successfully used in clinical practice for two conditions—infectious diarrhea and pouchitis secondary to ulcerative colitis surgery—backed by solid clinical trials data. But key questions remain regarding its use in IBS.