Efficacy and Safety of Probiotics in the Treatment of Irritable Bowel Syndrome
of VSL#3 on gastrointestinal transit and symptoms in 25 diarrhea- predominant IBS patients. No significant difference in mean gastrointestinal transit measurements or IBS symptoms was noted between the VSL#3 and placebo groups although a statistically significant decrease in abdominal bloating scores for VSL#3 versus placebo was identified (p<0.05).69
In a subsequent study by the same
group, VSL#3 was found to be associated with significantly reduced flatulence scores versus placebo (p=0.011) although the proportions of responders for satisfactory relief of bloating, stool-related symptoms, abdominal pain, and bloating scores were not different between the groups.70
placebo administration, respectively. However, in common with many other probiotic trials, the use of an unvalidated end-point adds a layer of complexity when trying to interpret these results. Furthermore, a subsequent study evaluating 24-hour gas production in IBS patients treated with the same Lactobacillus strain failed to show a difference in total gas production or symptom improvement versus placebo.31 Additional negative trials with Lactobacillus species have been reported75,77
and a recent meta-analysis by Moayyedi and co-workers reviewed four of the trials discussed above28,43,76,77
Although the authors concluded that VSL#3 is efficacious for treating flatulence and bloating, the small sample sizes and somewhat disparate results between the studies make it difficult to draw any definitive conclusions regarding the efficacy of VSL#3 in IBS.
SCM-III is another combination product comprised of three probiotics (L. acidophilus, L. helveticus, and Bifidobacterium spp.), which was evaluated by Tsuchiya and co-workers in 68 IBS patients.71
There was a
statistically significant improvement in overall efficacy at 12 weeks (p<0.01), as well as improvement in bloating, abdominal pain, and bowel habits at different time intervals throughout the 12-week period. However, this study was limited by its single-blinded design, small study population, and use of pseudo-randomization.
The efficacy of a probiotic mixture containing L. rhamnosus GG, B. breve Bb99, L. rhamnosus LC705, and Propionibacterium freudenreichii species. Shermanii JS was evaluated by Kajander and colleagues in 103 IBS patients.72
At the end of the study (24 weeks), the total symptom score (abdominal pain, distension, flatulence, rumbling) was significantly lower in the probiotic group compared with the placebo group (p=0.015), representing a median reduction in the symptom score of 42 and 6% in the probiotic and placebo groups, respectively. For individual symptoms, ‘rumbling’ was milder in the probiotic group (p=0.008), and for the rest of the symptoms non-significant positive trends were observed. A more recent study by the same authors using a similar probiotic mixture (containing B. animalis instead of B. breve) also showed a statistically significant difference in favor of the probiotic mixture for a composite symptom score (p=0.0083) at 20 weeks, with abdominal distension and bowel symptoms particularly improved.73
However, it should be noted
that, in common with many probiotic trials, both studies were limited by relatively small sample sizes.
Lactobacillus and Bifidobacterium Species Single strains of Lactobaccilli or Bifidobacteria have been used in the majority of probiotic trials. Studies assessing single strains of Lactobacillus spp. have yielded mixed results28,31,43,74–77
Halpern and
colleagues noted a statistically significant reduction in an IBS symptom index with L. acidophilus versus placebo74
and resolution of abdominal
pain was noted in 20 patients treated for four weeks with L. plantarum compared with 11 of 20 patients who received placebo.76
The efficacy of
L. plantarum has also been demonstrated in another randomized study that accrued 60 IBS patients.28
At the end of a four-week treatment
period it was noted that flatulence rapidly and substantially decreased in the L. plantarum versus the placebo group. The number of days with abundant gas production was 6.5 and 3.1 before and after L. plantarum treatment, respectively, while it was 7.4 and 5.6 before and after
US GASTROENTEROLOGY & HEPATOLOGY REVIEW
Clinical Safety of Probiotics in Irritable Bowel Syndrome
A major limitation of the majority of clinical studies evaluating probiotics in IBS is the lack of systematic recording of adverse events and tolerability. In their systematic review of RCTs of probiotics in IBS, Brenner and colleagues noted that only four of the 16 trials included in their analysis provided data on adverse events and that tolerability was not appropriately recorded in any of the studies.79
Furthermore, available 51 that evaluated single
strains of Lactobacillus and found no significant benefit in alleviating IBS symptoms in 200 patients when rigorous assessment of methodology and statistical designs of the studies was performed.78
The meta-analysis by Moayyedi and co-workers concluded that there was a trend for Bifidobacteria spp. to improve IBS symptoms, an observation corroborated by a separate systematic review by Brenner and co-workers.79
In this latter analysis, a review of 16 RCTs evaluating
probiotics in the treatment of IBS, B. infantis 35624 was the only probiotic to show significant improvements in IBS symptoms in appropriately designed studies. However, the two studies performed with this probiotic were of short duration and longer-term studies are required. In the first of these studies, IBS patients were randomized to receive either L. salivarius UCC4331, B. infantis 35624, or placebo. For all symptoms, with the exception of bowel movement frequency and consistency, those randomized to B infantis 35624 experienced a greater reduction in symptom scores; composite and individual scores for abdominal pain/discomfort, bloating/distention, and bowel movement difficulty were significantly reduced compared with those receiving placebo. This study also reported normalization of peripheral blood mononuclear cell cytokine levels in IBS patients with B. infantis 35624 but not with L. salivarius UCC4331, suggesting the possibility of an anti-inflammatory effect.43
The second study by Whorwell et al. was
a larger dose-ranging study of a duration of four weeks. Here, B. infantis 35624 at a dose of 108 CFU was found to offer significantly greater improvement in all of the primary symptoms as well as for global assessment of IBS symptoms at the end of therapy compared with placebo (p<0.02).80
B. infantis 35624 at a higher dose of 1010 CFU showed no benefit over placebo, but results may have been confounded by a formulation issue specific to this dose.
Initial evidence that B. animalis can improve IBS symptoms was provided in a randomized trial of 274 primary care adults with constipation- predominant IBS.81
B. animalis was shown to reduce bloating and improve stool frequency versus placebo and there was a significantly higher responder rate for the health-related quality of life discomfort score at three weeks in the B. animalis group compared with the placebo group (p<0.005).
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