Twenty-nine children (mean age 9.8 years, range 2-16 years) with newly diagnosed ulcerative colitis were randomly assigned to receive, in double-blind fashion, a probiotic preparation (VSL#3; 450 - 1,800 billion bacteria per day, based on patient weight) or placebo for one year. VSL#3 consists of four strains of lactobacilli, three strains of bifidobacteria, and one strain of Streptococcus salivarius subsp. thermophilus. All patients received glucocorticoids and mesalazine until remission occurred, and then continued to receive mesalazine as maintenance therapy. The proportion of patients who achieved remission was significantly greater in the probiotic group than in the placebo group (93% vs. 36%; p<0.001). After one year, the relapse rate was significantly lower in the probiotic group than in the placebo group (21% vs 73%; p=0.014). No adverse effects of VSL#3 were seen.
Comment by Alan Gaby, MD
It has been suggested that chronic infection plays a role in the pathogenesis of ulcerative colitis. In one study, facultatively enteropathogenic organisms such as Klebsiella spp. or Pseudomonas aeruginosa were found in colonic biopsy samples of nearly one-half of patients with ulcerative colitis. The possible role of bacterial infection in this disease is supported by a study in which colonic infusion (by retention enema) of fecal flora from healthy donors resulted in an apparent cure in six of six patients, with severe ulcerative colitis. The beneficial effect of probiotic treatment in the present study is presumably due to changes in the intestinal flora.
OBJECTIVES: Several probiotic compounds have shown promise in the therapy of ulcerative colitis (UC). However, a strong sustained benefit remains to be seen. Uncontrolled pilot studies suggest that a probiotic preparation (VSL#3) maintains remission in mild to moderate UC and reduces active inflammation in adult patients. Aims of our prospective, 1-year, placebo-controlled, double-blind study were to assess the efficacy of VSL#3 on induction and maintenance of remission and to evaluate the safety and tolerability of the probiotic preparation therapy in children with active UC. METHODS: A total of 29 consecutive patients (mean age: 9.8 years; range: 1.7-16.1 years; female/male: 13/16) with newly diagnosed UC were randomized to receive either VSL#3 (weight-based dose, range: 450-1,800 billion bacteria/day; n=14) or an identical placebo (n=15) in conjunction with concomitant steroid induction and mesalamine maintenance treatment. Children were prospectively evaluated at four time points: within 1 month, 2 months, 6 months, and 1 year after diagnosis or at the time of relapse. Lichtiger colitis activity index and a physician's global assessment were used to measure disease activity. At baseline, within 6 months and 12 months or at the time of relapse, all patients were assessed endoscopically and histologically. RESULTS: All 29 patients responded to the inflammatory bowel disease (IBD) induction therapy. Remission was achieved in 13 patients (92.8%) treated with VSL#3 and IBD therapy and in 4 patients (36.4%) treated with placebo and IBD therapy (P<0.001). Overall, 3 of 14 (21.4%) patients treated with VSL#3 and IBD therapy and 11 of 15 (73.3%) patients treated with placebo and IBD therapy relapsed within 1 year of follow-up (P=0.014; RR=0.32; CI=0.025-0.773; NNT=2). All 3 patients treated with VSL#3 and 6 of 11 (54.5%) patients treated with placebo relapsed within 6 months of diagnosis. At 6 months, 12 months, or at time of relapse, endoscopic and histological scores were significantly lower in the VSL#3 group than in the placebo group (P<0.05). There were no biochemical or clinical adverse events related to VSL#3. CONCLUSIONS: This is the first pediatric, randomized, placebo-controlled trial that suggests the efficacy and safety of a highly concentrated mixture of probiotic bacterial strains (VSL#3) in active UC and demonstrates its role in maintenance of remission.
Miele E, et. al. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol. 2009 Feb;104:437-443.
Reprinted with exclusive permission by Townsend Letter, July, 2009