Efficacy of probiotics for treatment of acute or persistent diarrhoea in children from birth till 10 years: Systematic review and meta-analysis.

Background: Numerous studies have investigated the efficacy of probiotics in treating acute and persistent diarrhoea. However, probiotics have not been established as a recommended management option for diarrhoeal illness by the World Health Organization (WHO). Therefore, we conducted a systematic review of randomised controlled trials to assess the efficacy of probiotics for the management of acute and persistent diarrhoea in children. Methods: A systematic search on PubMed, CINAHL, Wiley Cochrane Library, Scopus, Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform (ICTRP) was performed. All studies published in the year 2000 and onwards that assessed the use of probiotics in the management of acute and persistent diarrhoea in children aged 0-10 years were included. The risk of bias was assessed using the Cochrane Risk of Bias II (RoB-2) tool and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. This review was commissioned by WHO for revision of their guidelines for childhood diarrhoea management. Results: The review included 98 studies with a total of 17 236 participants. Studies were categorised based on the WHO definition of diarrhoea or author-specified definition. In studies considering the WHO definition of diarrhoea, the probiotics group was more likely to achieve clinical cure (risk ratio = 1.12 (95% confidence interval (CI) = 1.01, 1.24, studies = 14)) and reduce the duration of diarrhoea (mean difference = -13.27 hours (95% CI = -16.72, -9.83, studies = 33)) than the control group in children with acute diarrhoea. However, the effect size was small, and statistical heterogeneity was very high, leading to low certainty of evidence. In children with persistent diarrhoea, probiotics reduced the duration of diarrhoea by 95 hours (mean difference = -96.45 (95% CI = -110.53, -82.37, studies = 2)), but the certainty of the evidence was very low. Conclusions: The results from this systematic review suggest low certainty of evidence for the effect of probiotics on clinical cure and duration of diarrhoea in children. There was significant diversity in the genus, species, dosages, and duration of treatment in the trial and administration. High levels of heterogeneity reduced the certainty of evidence. Large-scale randomised clinical trials are needed to evaluate specific probiotic strains and doses. In addition, cost-effective analysis studies are needed to be explored in future research. Registration: The protocol for this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023449200).