The etiology of irritable bowel syndrome (IBS) is thought to be multifactorial, with several factors (including alterations in gut motility, small-bowel bacterial overgrowth, microscopic inflammation, and visceral hypersensitivity) potentially playing a role. Recent studies have suggested that probiotics may be useful in the treatment of IBS. Although the exact mechanism for how probiotics may aid in the reduction of symptoms commonly found in IBS is unknown, the effects of probiotics on alterations in gut bacteria appear to play a part. This review focuses on recent studies examining the role of probiotics in the treatment of IBS.
Iritable bowel syndrome (IBS) is a common disorder affecting millions of people worldwide. Over the past few years, there has been an emergence of new concepts related to the pathophysiology of IBS. These concepts include alterations in gut motility, small-bowel bacterial overgrowth, microscopic inflammation, visceral hypersensitivity, and changes related to the brain-gut axis. This changing paradigm may allow for probiotic therapeutic opportunities in IBS.
Probiotics are defined as “live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host.” This paper reviews the potential benefits of probiotics in patients with IBS.
Physiologic Benefits of Probiotics in Irritable Bowel Syndrome
Probiotics are live microorganisms with a vast array of therapeutic potential for gastrointestinal disease. They have been studied and used in many gastrointestinal disorders, with growing evidence for use in pouchitis, Clostridium difficile colitis, antibiotic-associated diarrhea, inflammatory bowel disease, and IBS. The emerging multifactorial pathophysiologic paradigm of IBS may create adjunctive probiotic therapeutic opportunities.
Probiotics have a beneficial effect on intestinal mucosa via several proposed mechanisms that include suppression of the growth and binding of pathogenic bacteria, improvement of the barrier function of the epithelium, and alteration of the immune activity of the host. Probiotics secrete short chain fatty acids, an action that results in decreased luminal pH and production of bactericidal proteins. Butyric acid, a byproduct of bacterial fermentation of fiber, has been shown to nourish colonic enterocytes, enhancing mucosal integrity. The DNA of probiotic organisms has also been shown to inhibit apoptosis of epithelial cells. In addition, probiotics may improve bowel dysmotility.
A study by Desbonnet and coworkers investigated the probiotic Bifidobacterium infantis on rats that were chronically subjected to a stressor (a forced swim test) for 14 days. The results were reductions in the levels of tumor necrosis factor alpha, interferon gamma, and interleukin 6 after stimulation of peripheral blood monocytes. Plasma levels of tryptophan and kynurenic acid were also significantly increased in the rats treated with B. infantiscompared to controls. There was no improvement in performance during the stressor, though B. infantis may have had a role as an antidepressant by increasing the levels of tryptophan, a serotonergic precursor, and reducing pro-inflammatory markers. These raised levels of tryptophan can potentially reduce depressive overlay and aberrant enteric nervous system effects in IBS.
Studies on Probiotics
There is a limited amount of quality evidence for the empiric use of probiotics in IBS. The randomized controlled trials that have been performed are typically small and are limited by publication bias. Previous trials have typically included strains of Lactobacillus species, Bifidobacterium species, and Propionibacterium species, along with different probiotic combinations such as VSL#3 and SCM-III.
Kim and colleagues performed two double-blind, pla-cebo-controlled trials examining VSL#3 for the treatment of IBS symptoms. VSL#3 is a combination of probiotics that contains live bacteria including Bifidobacterium(B. longum, B. infantis, and B. breve); Lactobacillus (L. acidophilus, L. casei, L. delbrueckii ssp. bulgaricus,and L. plantarum); and Streptococcus salivarius ssp. thermophilus. The first trial by Kim, in 2003, evaluated the effect of VSL#3 on gastrointestinal transit and symptoms of diarrhea-predominant IBS. Twenty-five IBS patients were randomized to receive VSL#3 or placebo for 8 weeks. With VSL#3, the decrease in bloating was borderline significant, but there was no effect on gastrointestinal transit or other individual symptoms of IBS. Kim and associates performed a second placebo-controlled trial studying VSL#3 and its effects on IBS symptoms and colonic transit in 48 IBS patients, with abdominal bloating as the primary endpoint. VSL#3, as compared to placebo, led to a reduction in flatulence and a delay in colonic transit.
SCM-III is another probiotic combination of 3 different strains (L. acidophilus, Lactobacillus helveticus, and Bifidobacterium sp.), which was evaluated by Tsuchiya and coworkers in a study of 68 IBS patients. The study participants were randomly assigned to receive SCM-III or placebo for 12 weeks. There was an improvement in overall efficacy in 80% of patients at 12 weeks (P<.01), as well as improvement in bloating, abdominal pain, and bowel habits at different time intervals throughout the 12-week period. However, the limitations of this study included its single-blinded design, small study population, and use of pseudo-randomization.
Lactobacillus and Bifidobacterium Species
Saggioro performed a study with 70 IBS patients, randomizing them to 3 different treatment groups for assessing improvements in abdominal pain and severity scores of 7 IBS symptoms. These treatment arms included Group 1 (L. plantarum LP01 and B. breve BR0); Group 2 (L. plantarum LP01 and L. acidophilus LA02); or placebo. Both treatment cohorts showed significant decreases in abdominal pain and severity scores at 2 and 4 weeks; however, the major limitation of this study was the inability to perform statistical evaluation due to its small number of patients and its short duration of follow-up.
O’Mahony and associates performed a study in 77 patients diagnosed with IBS (based upon Rome II criteria) and grouped them into 3 different treatment arms. The patients received Lactobacillus salivarius UCC4331, B. infantis 35624, or placebo for a total of 8 weeks and then were assessed for the cardinal symptoms of IBS (abdominal pain/discomfort, bloating/distension, and difficulty of bowel movement), quality of life, and blood sampling for interleukin-10 and -12. Those patients randomized to the B. infantis 35624 arm showed a significant reduction in composite symptom score as well as a reduction in each individual symptom, with the exception of bowel movement frequency and consistency. The interleukin-10/-12 ratio, which is abnormal in IBS patients in the proinflammatory state, was normalized in the B. infantis 35624 arm, suggesting that the mechanism of action of this particular probiotic may have an immune-modulating effect. The limitations of this trial, as with other trials involving probiotics, include its small size and lack of power calculation; otherwise, it was a well-designed trial. The authors concluded that additional larger, randomized, controlled trials studying B. infantis 35624 are needed, along with further research regarding the mechanism of immune regulation in IBS patients.
A larger study by Whorwell and coworkers evaluating different doses of B. infantis 35624 was performed in 362 women diagnosed with IBS.39 The study participants were randomized to low or high doses of B. infantis or placebo and were followed for a total of 4 weeks. In the treatment group, there was a significant decrease in abdominal pain/discomfort (the primary endpoint) at 4 weeks, along with improvement in the secondary endpoints of bloating/distension, sensation of incomplete evacuation, passage of gas, straining, bowel habit satisfaction, and a reduction in composite symptom score. These benefits were only noted in the high-dosing group containing 1 × 10*10 CFU/mL of B. infantis, and not 1 × 10*8 CFU/mL of B. infantis. The authors concluded that the discrepancy in the efficacy of the higher and lower concentrations may have been secondary to the methods that the different formulations use to release the active agent within the intestine.
A study by Guyonnet and colleagues assessed 274 constipation-predominant IBS patients and randomized them to placebo or fermented milk yogurt (Activia, Dan-non), which contains Bifidobacterium animalis (regularis)DN-173 010 for 6 weeks. In the treatment group, the health-related quality-of-life discomfort score improved, as well as bloating symptoms (both of which were primary endpoints), and there was an increase in stool frequency in patients with fewer than 3 stools per week. This yogurt (ie, B. regularis) may have promotility benefits for the alleviation of IBS bowel dysmotility and may shorten intestinal transit time.
Past studies involving the Lactobacillus species as either a single probiotic agent or in combination with other probiotics have been less impressive. A 6-month double-blind, placebo-controlled study by Kajander and associates evaluated 103 patients with IBS and randomized them to a probiotic mixture containing Lactobacillus rhamnosus GG, L. rhamnosus LC705, B. breve Bb99, and Propionibacterium freudenreichii ssp. shermaniiJS, or to placebo and then followed them for 6 months. A 44% reduction in the symptom score (consisting of abdominal pain, distension, flatulence, and borborygmi) was seen in the probiotic group at the end of the trial. A recent meta-analysis by Moayyedi and coworkers reviewed 4 trials evaluating single strains of Lactobacillus and found no significant benefit in alleviating IBS symptoms in 200 patients.
Nine trials evaluated different probiotic combinations (most often including Bifidobacterium, Lactobacillus, and Streptococcus) in 772 patients and showed a significant effect in improving IBS symptoms. Two trials involving Bifidobacterium, conducted by O’Mahony and associates and Whorwell and colleagues (both of which were previously mentioned in this article), were included in this meta-analysis and showed a trend toward improving IBS symptoms in 379 patients.
Brenner and coworkers conducted a meta-analysis in 2009 that included 16 randomized controlled trials evaluating the efficacy, safety, and tolerability of probiotics in IBS patients. B. infantis 35624 was the only probiotic that showed any significant benefit in the composite symptom score of IBS patients. Bifidobacterium likely has a beneficial effect in the symptom relief of IBS either as a single agent or in combination with other probiotics, though the available data are inadequate and further well-designed trials are still needed.