Bacillus clausii as adjunctive treatment for acute community-acquired diarrhea among Filipino children: a large-scale, multicenter, open-label study (CODDLE)

Abstract

Background Diarrhea is among the main causes of pediatric mortality in the Philippines. Probiotics have been shown to be beneficial in the management of acute diarrhea. Accordingly, the aim of this population-based study was to assess the safety and effectiveness of Bacillus clausii as an adjunct to standard therapy in Filipino children with acute community-acquired diarrhea of viral origin or associated with antibiotic administration. Methods A total of 3178 patients (median age of 2 years) were enrolled in this open-label, multicenter, observational study, and were treated with one to two vials of Bacillus clausii in the following bacterial stains: O/C, SIN, N/R, and T (oral suspension of 2 billion spores per 5-mL vial) for 5 to 7 days. Diarrhea duration, number of stools per day, improvement in gastrointestinal symptoms, children’s overall acceptability of Bacillus clausii therapy, and safety and tolerability were assessed. Concomitant treatment with oral rehydration solutions (26.6%), zinc (23.9%), and antibiotics prescribed for conditions other than diarrhea (13.6%) was recorded during the study. All other probiotics and antidiarrheals were prohibited. Results Therapy with Bacillus clausii was well-tolerated, and the adverse event rate was very low (0.09%). All reported adverse events, which included vomiting, erythematous rashes and stool color change, were mild to moderate. In more than half of the per-protocol population (1535/2916; 52.6%), diarrhea was resolved within the first 3 days of treatment with Bacillus clausii . There was no significant difference ( p = 0.297) in mean diarrhea duration between patients with either antibiotic-associated (3.3 ± 1.3 days) or viral diarrhea (3.4 ± 1.3 days). However, children who only received Bacillus clausii supplementation without zinc had a significantly shorter diarrhea duration (3.3 ± 1.3 days) compared to zinc-treated children (3.6 ± 1.6 days; p < 0.001). Bacillus clausii significantly reduced the mean number of stools per day, from 5.2 ± 2.0 stools at baseline to 1.2 ± 0.6 stools at study end ( p < 0.001). Similarly, the proportion of patients with loose stools decreased from 81.6% at baseline to 9.2% at end of treatment period. Acceptability of Bacillus clausii therapy was high. Conclusion This study adds knowledge on the good safety profile and on the effectiveness of Bacillus clausii as an adjunct treatment for acute childhood diarrhea.

Protective action of Bacillus clausii probiotic strains in an in vitro model of Rotavirus infection

“…There was also a trend towards a reduction in stool frequency. In line with the findings of the meta-analysis, data from a large observational study indicated a reduction in diarrhea duration (median duration 3 days) and stool frequency in children with viral or antibiotic-associated AGE who were treated with the O/C, T, SIN, N/R mix of B. clausii strains 28 . There was no significant difference in the mean duration of diarrhea between patients with viral diarrhea and those with antibiotic-associated diarrhea.…”

“…Although a specific recommendation for B. clausii in the treatment of childhood AGE has hitherto been missing because of limited data, there is now a growing body of clinical evidence in support of the O/C, T, SIN, N/R mix of B. clausii probiotic strains as an effective therapeutic option in this clinical setting 13,28,30 . Modulation of the immune response with this B. clausii strains mix may also have health benefits beyond the treatment of AGE, ranging from the prevention of recurrent respiratory infections in allergy-prone children to influencing outcomes in cancer patients 31,32 .…”

“…Modulation of the immune response with this B. clausii strains mix may also have health benefits beyond the treatment of AGE, ranging from the prevention of recurrent respiratory infections in allergy-prone children to influencing outcomes in cancer patients 31,32 . In addition to its documented efficacy and safety in childhood AGE 13,28 , B. clausii www.nature.com/scientificreports/ has the practical advantage of being a spore-forming probiotic, making it heat stable and able to be transported and stored at room temperature without loss of viability 33 . Given that certain effects of probiotics, including immunomodulatory effects, are likely to be strain-specific 11 , a key strength of our study and the aforementioned clinical studies is that a clearly defined mix of four B. clausii strains was used.…”

“…Modulation of the immune response with this B. clausii strains mix may also have health benefits beyond the treatment of AGE, ranging from the prevention of recurrent respiratory infections in allergy-prone children to influencing outcomes in cancer patients 31 , 32 . In addition to its documented efficacy and safety in childhood AGE 13 , 28 , B. clausii has the practical advantage of being a spore-forming probiotic, making it heat stable and able to be transported and stored at room temperature without loss of viability 33 .…”

Effect of Physical and Chemical Treatments on Viability, Sub-Lethal Injury, and Release of Cellular Components from Bacillus clausii and Bacillus coagulans Spores and Cells

“…As B. clausii is highly resistant to most antibiotics, its efficacy is not altered by concomitant antibiotherapy. Moreover, B. clausii is unique by its fast growth in aerobic and anaerobic environments [16].…”