Journal of Pediatric Gastroenterology & Nutrition:
Letters to the Editor
Shulman, Robert J.; Smith, E. O’Brian
Baylor College of Medicine, Houston, TX
To the Editor: We read with great interest the report by Guandalini et al (1) on the effectiveness of the probiotic VSL#3 in improving symptoms in children with irritable bowel syndrome (IBS). A number of issues, however, impair interpretation of the results. The crossover design of the study is extremely problematic. A number of studies evaluating probiotics have shown that their beneficial effects on IBS symptoms extend weeks beyond the treatment period (2–5). In patients with ulcerative colitis, VSL#3 exerts a significant effect on stool pH at least 15 days after administration ceases, a time when the organisms are no longer recoverable in feces based on studies in patients with IBS, even with using older methodology (6,7). Thus, there likely was a carryover effect between the 2 study periods, clouding interpretation of the results. Indeed, this is one of the reasons that an expert panel does not recommend the use of crossover trials for IBS (8). Additional causes of concern include lack of a CONSORT flow diagram, lack of intention-to-treat data analysis, and failure to use a 2-way analysis of variance (to account for group).
1. Guandalini S, Magazzu G, Chiaro A, et al. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr 2010;51:24–30.
2. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 2005; 128:541–551.
3. Guglielmetti S, Mora D, Gschwender M, et al. Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life—a double-blind, placebo-controlled study. Aliment Pharmacol Ther 2011; 33:1123–1132.
4. Kajander K, Myllyluoma E, Rajilic-Stojanovic M, et al. Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther 2008; 27:48–57.
5. Williams E, Stimpson J, Wang D, et al. Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther 2009;29:97–103.
6. Venturi A, Gionchetti P, Rizzello F, et al. Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 1999; 13:1103–1108.
7. Brigidi P, Vitali B, Swennen E, et al. Effects of probiotic administration upon the composition and enzymatic activity of human fecal microbiota in patients with irritable bowel syndrome or functional diarrhea. Res Microbiol 2001; 152:735–741.
8. Irvine EJ, Whitehead WE, Chey WD, et al. Design of treatment trials for functional gastrointestinal disorders. Gastroenterology 2006; 130:1538–1551.