Efficacy and Safety of the Adjuvant Use of Probiotic Bacillus clausii Strains in Pediatric Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Objectives Current irritable bowel syndrome (IBS) treatments have limited efficacy and probiotics like Bacillus clausii ( B. clausii ) were found to be effective in the management of several gastrointestinal disorders. This phase III trial assessed the efficacy and safety of adding B. clausii (four strains: O/C, N/R, SIN, T), versus placebo, to conventional treatment of pediatric IBS in Mexico. Methods Patients aged 6–17 years 11 months with IBS (Rome IV) for at least 2 months were randomized to receive either B. clausii (oral suspension, total dose 4 billion spores/day) or placebo once daily for 8 weeks. All patients also received conventional treatment. The primary endpoint was the difference in the proportion of patients with clinical improvements at Week 8 (Global Assessment Questions [GAQ]). Secondary endpoints included responders by Subject’s Global Assessment of Relief for Children with IBS (SGARC); number/consistency of stools; abdominal distention/bloating; abdominal pain/intensity; and IBS behavior. Results 73.6% (95% confidence interval [CI] 67.3–80.0; B. clausii n = 129) and 78.5% (95% CI 72.5–84.4; placebo n = 130) of patients had symptom improvement ( p = 0.8182). For Week 8 SGARC, 19.2% ( B. clausii ) and 20.9% (placebo) reported complete symptom relief. Stool evaluations, bloating, abdominal pain/intensity, and IBS behavior were similar between groups. Both treatments were well tolerated. Conclusion No significant differences in efficacy between B. clausii and placebo were demonstrated in addition to conventional treatment. The sample size calculation was based on an expected placebo/conventional treatment response of 30–40%. However, the actual treatment response observed was 80% and, thus, a study with larger population would be warranted. In addition, this study was conducted during the COVID-19 pandemic, when such controlled social conditions may have resulted in better diet, greater family stability, less psychological stress, and lower risk of infections exacerbating IBS, thereby improving symptoms in both groups. EudraCT number 2018-004519-31. Supplementary Information The online version contains supplementary material available at 10.1007/s40272-022-00536-9.

Efficacy of probiotics, prebiotics and synbiotics in irritable bowel syndrome: a systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials

“…Full-text screening was conducted in the remaining 150 articles. We identified 46 studies of probiotic therapy in IBS [16–59], three studies of prebiotics [60–62] and three studies of synbiotics [63–65]. Finally, 50 articles reporting 52 studies were included in this meta-analysis.…”

“…Therapeutic dosage of probiotics for each study was extracted for further analysis, and we only included studies reporting probiotic dosage in c.f.u. or that could be converted into c.f.u./day [17, 18, 21, 22, 25, 28, 34–47, 51, 52, 55, 56, 59] (). Trials, in which the dosages of probiotics were changed during the intervention period were excluded from the subgroup analysis [23, 24, 32, 33].…”

“…In low-dosage group (10 8 c.f.u./day ≤ dose<10 9 c.f.u./day), there was no significant difference on the efficacy between probiotics and placebo (RR:2.90, 95 % CI:0.38–22.20, P =0.31) [40, 52]. As for the high-dosage group (≥ 10 9 c.f.u./day), the effect of probiotics on treatment response was markedly superior to that of placebo ( I 2 =84 %, P <0.00001; RR:1.62, 95 % CI:1.29–2.04, P <0.0001) [17, 18, 21, 22, 25, 28, 34–39, 41–47, 51, 55, 59].…”

What is new with irritable bowel syndrome

“…They found a significant decrease in the severity of abdominal pain with probiotic use, especially if the treatment duration exceeded 4 weeks [17 ▪ ]. Although the study by Vazquez-Frias et al [16 ▪ ] did not show any significant benefit of probiotics when compared with placebo, they still found that most of the patients treated with probiotics had symptom improvement. Additionally, the meta-analysis by Fatahi et al [17 ▪ ] showed that probiotic supplementation has the potential to reduce abdominal pain in patients with IBS.…”

“…This was in addition to conventional treatment such as diet, laxatives, analgesics, and antispasmodics. They found that 73.6% of participants in the treatment group and 78.5% of participants in the placebo group had clinical improvement in symptoms [16 ▪ ]. In another study, Fatahi et al conducted a systematic review and meta-analysis of RCTs as far back as April 2021 to evaluate the effectiveness of probiotic supplementation on abdominal pain severity in IBS, which included seven RCTs, totaling 441 participants.…”