Probiotics
Table 1: Studies on the Use of Probiotics in Pediatric Inflammatory Bowel Disease Study
Disease Miele et al., 200916
Huynh et al., 200917 Henker et al., 200815 Bousvaros et al., 200529
Mild to moderate UC Control Group Probiotic
Mild to moderate acute UC None Inactive UC CD
Dose (Daily) Duration
5-ASA (n=10) EcN (n=24) Placebo (n=36) LGG (n=39)
VSL#3 (n=13) 225–1,125x109 (age) 8 weeks 5x1010
1x109 twice a day 5-ASA = 5-aminosalicylic acid; CD = Crohn’s disease; EcN = Escherichia coli Nissle; LGG = Lactobacillus GG; UC = ulcerative colitis;
on the use of VSL#3 in inducing remission in children with mild to moderate acute UC. Thirteen patients completed an eight-week treatment with VSL#3 while allowed to maintain stable oral doses of 5-ASA, steroids, or immunosuppressive agents. Remission was achieved in 56% of patients. Post-VSL#3 treatment showed a reduced bacterial taxonomy in rectal biopsy. This study was limited by a lack of placebo arm. Overall, current data do not allow recommending probiotics in the induction of UC. However, their use in maintenance therapy is more promising and needs to be further studied before it may be a proposed treatment. Table 1 summarizes studies available in children.
Pouchitis
Multiple studies on the use of probiotics in pouchitis, a possible complication following total colectomy, have been conducted in adults. In a randomized, double-blind, placebo-controlled trial, Gionchetti et al. showed that probiotics administration within one week after ileostomy closure is effective in the prevention of the onset of acute pouchitis.18 Mimura et al. published data proving the efficacy of VSL#3 in maintaining remission in antibiotic-sensible pouchitis.19
Therefore, a
strong body of evidence exists to support the use of probiotics as a therapeutic option in adult pouchitis. However, no study has been published in children. Therefore, there is currently insufficient evidence to recommend their use in children.
Crohn’s Disease
In adult CD, most studies have failed to show any beneficial effect of probiotics both in induction or maintenance therapy. In terms of induction therapy, only two placebo-controlled studies are available.20,21 Both studies found no significant difference in the time needed to induce therapy in the two groups. As for studies in maintenance therapy, one small randomized trial with Saccharomyces boulardii showed a significant reduction in the number of patients suffering from relapse in the combined mesalamine–probiotic group.22
However, these
promising findings have not been confirmed by other trials. A Cochrane review on probiotics for maintenance of remission in CD concluded that there is no evidence to suggest that probiotics are beneficial for the maintenance of remission in CD.23
Probiotics have also been studied in post-operative patients with CD.24 However, a recent meta-analysis on the use of probiotics in post- surgical patients with CD was not associated with any significant difference in risk of recurrence compared with placebo.25
Desreumaux et al.26 presented in an abstract the results of a randomized, double-blind, placebo-controlled trial using Lactobacillus 56
casei strain for the prevention of post-operative recurrence of CD. This probiotic was well tolerated over a one-year period, but did not prevent endoscopic and clinical recurrences after surgery.
There are limited data available about probiotics and CD in children. Very limited and preliminary data published in the early 2000s appeared to show that Lactobacillus GG could be helpful in improving the clinical status of children with mild to moderate Crohn’s disease.27,28 However, a randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard therapy for children with CD was published in 2005. Bousvaros et al.29
recruited 75 children who were
randomized to receive either Lactobacillus GG (10 billion units twice a day) or placebo for up to two years. Lactobacillus GG, used as an adjunct therapy, did not decrease relapse rate or prolong time to relapse in children with CD. As previously noted, a Cochrane review found no evidence to support the use of probiotics for the maintenance of remission in CD when it analyzed available data in both adults and children. Finally, there are no data available regarding induction therapy using probiotics in pediatric CD. Compared with UC, CD has obviously a wider spectrum of locations. Therefore, the presumed benefits of probiotics on a small bowel disease compared with a pure colonic disease may be completely different. As stated earlier, the distal ileum and the colon are the sites with the highest concentration of bacteria. One could also presume that these areas are the areas where the effects of probiotics could the most beneficial. Therefore, studies on CD will need to better identify the locations of disease involved. Also, similar to studies in UC, more variety of probiotics and different combinations of probiotics need to be trialled in patients with CD; to date most studies conducted in CD have mainly been using Lactobacillus. Certain probiotics strains seem more effective than others and, again, further studies will need to be directed as such.
Conclusion
Research on the use of probiotics in IBD is a growing phenomenon. Strong evidence regarding their beneficial effect in children with IBD is not yet available. There are no data in adult or children supporting the use of probiotics in induction, maintenance, or post-operative therapy for CD. As for UC, there is a growing body of evidence suggesting a possible benefit of probiotics as an adjunct treatment to standard therapy in maintenance of remission. Similar to adults, preliminary data from children also support probiotics use in maintaining remission. Available data in children have not clearly proved that probiotics are beneficial in inducing remission in UC. Evidence in adults from the literature seems to support the use of probiotics in pouchitis, but to date no trial has been performed in children. Large, multicenter, randomized controlled trials in children
US GASTROENTEROLOGY & HEPATOLOGY REVIEW Effect of Probiotics
Placebo (n=15) VSL#3 (n=14) 450–1,800x109 (weight) 12 months Efficacy as adjunctive therapy for induction and maintenance Remission in 56% of children
12 months As effective as low dose of 5-ASA 24 months No effect on relapse rate
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