Probiotics for irritable bowel syndrome.

History and Rationale for Use

The concept of probiotics as beneficial for intestinal health began with Nobel Prize-winning Russian scientist Ilya Ilyich Mechnikov. He viewed the large intestine as a vestigial organ that harbored dangerous, putrefaction-inducing bacteria, and believed that introducing lactobacilli into the body would promote health. The longevity of Balkan peasants, he wrote in "The Prolongation of Life: Optimistic Studies" in 1907, was likely a result of their consumption of fermented milk products.

A century later much is known about gut function, the 400 species of bacteria that reside in the colon, and host-flora interactions, including communication between intestinal microbes and the immune system. For instance, the host's immune system can differentiate between pathogenic bacteria and commensals through pattern recognition receptors and Toll-like receptors (TLRs). TLR2 triggers an immune response to gram-positive bacteria and yeasts, TLR4 mediates responses to lipopolysaccharides from gram-negative bacteria, and TLR9 recognizes certain sequences of bacterial DNA (Dig. Dis. 2006;24:137-47).

The currently accepted definition of probiotics is "nonpathogenic microorganisms, which, when ingested as living cells, exert a positive influence on host health or physiology" (Dig. Dis. 2006;24:137-47). The Lactobacillus and Bifidobacterium genera of bacteria are the most widely tested and commonly used probiotics.

There are several reasons why certain probiotic organisms could have beneficial effects in irritable bowel syndrome (IBS). Many have antiviral and antibacterial effects, which could be important in the 15%-25% of patients whose IBS dates from an episode of infectious gastroenteritis. Also, probiotics have anti-inflammatory effects on mucosal surfaces. By reducing gut mucosal inflammation, these organisms could decrease immune mediated activation of enteric neurons and thus alter neural traffic between the gastrointestinal tract and the central nervous system. Moreover, probiotics could quantitatively and qualitatively alter the gut flora, change the volume and composition of stool and gas, and increase secretion of intestinal mucus (Gastroenterology 2005;128:541-51).

Clinical Trials

Two studies done at the Mayo Clinic, Rochester, Minn., used a composite probiotic (VSL#3, manufactured by VSL Pharmaceuticals). The first study included 25 patients with diarrhea-predominant IBS who received VSL#3 powder (450 billion lyophilized bacteria per day) or placebo twice daily for 8 weeks. There was a borderline significant difference between the active and placebo groups on abdominal bloating, but no differences in gastrointestinal transit time, bowel function scores, or global symptom relief (Aliment. Pharmacol. Ther. 2003;17:895-904).

In the second trial, 48 patients were randomized to receive either the active treatment or placebo for up to 8 weeks. Mean posttreatment scores for symptoms including abdominal pain, flatulence, and bloating were numerically lower in the active treatment group, but only the score for flatulence achieved statistical significance. A total of 46% of patients in the active treatment group and 33% of patients in the placebo group had satisfactory relief for half of the weeks (J. Clin. Gastroenterol. 2006;40:264-9).

Another research group, led by Dr. Eamonn Quigley, professor of medicine at University College Cork (Ireland), randomized 362 women with IBS of any subtype to receive either placebo or one of three doses of encapsulated B. infantis (1 x [10.sup.6], 1 x [10.sup.8], or 1 x [10.sup.10] colony-forming units per milliliter) each day for 4 weeks.

On the primary end point, abdominal pain/discomfort at week 4, only the 1 x [10.sup.8] group had significant improvements, compared with baseline. Patients in this group also had significant improvements on the secondary outcomes of bloating/distention, sense of incomplete evacuation, passage of gas, straining, and bowel habit satisfaction (Am. J. Gastroenterol. 2006;101:1581-90).

A Role for Inflammation

In another study, 75 patients were randomized to receive either 1 x [10.sup.10] of L. salivarius or B. infantis in a malted milk drink or a malted milk placebo for 8 weeks. On the three cardinal symptoms of IBS--abdominal pain/discomfort, bloating or distention, and bowel movement difficulty, the Bifidobacterium was superior to the Lactobacillus, and the therapeutic gain of 20%-25% over placebo was equivalent to that reported for tegaserod (Gastroenterology 2005;128:541-51).

In this study, the investigators also measured peripheral blood cytokine levels and reported that, compared with normal controls, baseline levels of interleukin (IL)-10 were low and levels of IL-12 were increased, a ratio that is skewed toward a proinflammatory cytokine profile. This ratio returned to normal among patients in the B. infantis group, but not in the L. salivarius group or the normal controls.

The authors wrote that in this study, "by demonstrating a normalization of the IL-10/IL-12 ratio in the bifidobacteria-fed subjects alone, and in parallel with symptomatic improvement, we provide the first evidence for efficacy for an anti-inflammatory approach in IBS."

Advice From an Expert

Much confusion exists regarding the use of probiotics for IBS, with many substandard studies and exaggerated claims, according to Dr. Quigley, who is also vice president of the World Gastroenterology Organisation. In an interview, he noted that few probiotics have been subjected to high-quality clinical trials. He also pointed out that quality control is a real issue.

"Many of the probiotics on the shelf cannot be validated in terms of constituents, dose, viability, properties, efficacy, lack of contamination, and shelf-life," he noted. Finally, he cautioned that probiotics differ: "No two are exactly the same. Extrapolations from one, even if closely related, cannot and should not be made."

RELATED ARTICLE

* Theoretical reasons why probiotics could be beneficial in irritable bowel syndrome include anti-inflammatory effects and immune modulation in the gut.

* Clinical trial data remain sparse, and quality control is problematic.