Effects of spore-forming probiotic Bacillus subtilis HU58™ in children with antibiotic-associated diarrhoea: a randomised, double-blind, placebo-controlled trial.

Antibiotics are among the most prescribed medicines in children globally. Antibiotic-associated diarrhoea (AAD) and associated abdominal pain are common side effects, caused by alterations to the intestinal microbiota composition. Most research on probiotic interventions involves prophylactic use of Saccharomyces, lactobacilli or bifidobacteria. Less is known about spore-forming strains administered after AAD onset. Bacillus subtilis HU58™ was found to improve AAD symptoms in adults. This randomised, double-blind, placebo-controlled trial in India investigated the effects of a dietary supplement containing B. subtilis HU58 (2 × 109 cfu/day) versus placebo for seven days on diarrhoea duration (Bristol Stool Scale, BSS), abdominal pain intensity (Visual Analogue Scale, VAS), and overall gastrointestinal wellbeing (adapted Gastrointestinal Restoration Questionnaire, GIRQ; Physician Global Assessment, PGA) in 68 children (1-12 years) with AAD. Between-group comparison of data from each timepoint was conducted for the intention to treat population (Chi-squared test of independence for distribution of BSS types, Wilcoxon rank sum test for mean BSS types, mixed model for repeated measures for VAS, GIRQ and PGA scores). By day 3, 93.5% of the probiotic group had normal BSS types, versus 22.6% in the placebo group ( P < 0.001). Almost all subjects in both groups had normal stool types by day 7. Significantly greater decreases in abdominal pain VAS scores were observed among those receiving the probiotic versus placebo at day 3 (-7.4 [SE 0.5] versus -1.9 [SE 0.3], P < 0.001) and day 7 (-9.1 [SE 0.3] versus -8.5 [SE 0.2], P < 0.001). Greater improvements for both adapted GIRQ and PGA scores assessing GI wellbeing were observed in the probiotic group compared to the placebo group at days 3 and 7 (all P < 0.001). Spore-forming B. subtilis HU58 administered to children after onset of AAD may lead to faster resolution of diarrhoea and associated abdominal pain. Further research with daily clinical assessment and faecal microbiome analysis is warranted. The trial is registered at https://ctri.nic.in/Clinicaltrials (CTRI/2022/02/040138).